Express Pharma (Vol.16, No.10) September 2021

VOL. 16 NO. 10 PAGES 76

www.expresspharma.in

INTERVIEWS Dr Arun Chandavarkar Managing Director Biocon Biologics Vipin Choudhary Founder and CEO PUCHO

SEPTEMBER 2021, ` 40

CONTENTS

Chairman of the Board Viveck Goenka Sr. Vice President-BPD Neil Viegas Asst. Vice President-BPD Harit Mohanty Editor Viveka Roychowdhury* BUREAUS Mumbai Lakshmipriya Nair, Kalyani Sharma

DISSO INDIA 2021 ONLINE: TRACKING ADVANCEMENTS IN DISSOLUTION SCIENCE AND ITS APPLICATIONS The international conference of Society for Pharmaceutical Dissolution Science (SPDS) was conducted online in collaboration with AAPS, US on the theme, 'Dissolution as a Pivotal Tool for Drug Product Performance' | P14

MARKET

STARTUP

STRATEGY

PHARMAPACKAGING

Delhi Akanki Sharma DESIGN Asst. Art Director Pravin Temble Senior Designer Rekha Bisht Senior Artist Rakesh Sharma

P34:INTERVIEW Rrajesh Khosla President and CEO, AGI glaspac

Digital Team Viraj Mehta (Head of Internet) Marketing Team Rajesh Bhatkal Ambuj Kumar Ashish Rampure Debnarayan Dutta

P12:INTERVIEW

PRODUCTION General Manager BR Tipnis

Dr Arun Chandavarkar Managing Director, Biocon Biologics

Production Co-ordinator Dhananjay Nidre Scheduling & Coordination Arvind Mane CIRCULATION Circulation Team Mohan Varadkar

31

IMPACT OF COVID-19 AND REGULATIONS FOR OTC SEGMENT

P32:INTERVIEW Vipin Choudhary Founder and CEO, PUCHO

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Editor: Viveka Roychowdhury.* (Editorial & Administrative Offices: Mafatlal Centre, 7th floor, Ramnath Goenka Marg, Nariman Point, Mumbai 400021) * Responsible for selection of news under the PRB Act. Copyright © 2017. The Indian Express (P) Ltd. All rights reserved throughout the world.

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EDITOR’S NOTE

Is India’s pharma sector being penalised for its success?

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ndia Pharma Inc was in for a rude shock on August 17 when the Government of India finally announced the rates of rebate under the Remission of Duties and Taxes on Exported Products (RoDTEP) scheme.

The pharma sector, along with chemicals and steel, has been left out of RoDTEP, which would be effective from January 01, 2021. Ostensibly, because India enjoys global competitiveness in these sectors, but it is more likely that the government would like to discourage or at least not do anything to make exports easier in sectors where there is a short supply in the domestic market.

And the pharma sector certainly meets this description. A case in point is COVID vaccines, where output still does not meet demand. Beyond vaccines, the government is currently engaging all stakeholders to create and maintain a pool of essential medicines and medical products to prepare for future waves. Clearly, the message seems to be that managing the COVID-19 situation in India takes precedence over exports.

Industry associations like the Indian Pharmaceutical Alliance (IPA) have registered their protest. Sudarshan Jain, Secretary-General, IPA asserts that the pharma industry deserves three to six per cent benefit both for API and formulations.

The IPA has emphasised this point to the relevant committee, says Jain.

The IPA’s contention is that the exclusion of pharma exports from the RoDTEP scheme will adversely impact the pharma sector's competitiveness, depriving pharma exporters of a level playing field vis-a-vis global manufacturers.

Jain points out that competition is increasing from various countries and it is important to provide a level playing field to the sector to maintain a competitive position and leverage the potential of the industry.

The IPA statement alludes to the highly regulated nature of the sector and the need for huge capital investment to set up manufacturing infrastructure.

In fact, the IPA argues that ‘for sustaining India’s export competitiveness, RoDTEP benefits should be extended to the pharma sector given the importance of the sector in access of affordable medicine to patients in India and around the world.’

It follows that pharma exports set off the costs of providing affordable medicines in India. Seen in that light, it would make sense to extend the RoDTEP scheme to the sector, but the government is evidently

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Leaving out pharma from the RoDTEP scheme is harsh but the message is that managing the COVID-19 situation in India takes precedence over exports

worried that medicines and vaccines meant for India will be diverted to exports.

The country’s COVID vaccine coverage is still low.

According to the Our World in Data site, as of August 24, 2021, just 9.42 per cent of India’s population has had two doses, while 23.35 per cent have had a single dose. With just 32.77 per cent of our population vaccinated with one or two doses, talk of a third booster dose seems counterintuitive.

So will the government consider the industry’s argument, given that exports have been a high thrust area? As IPA’s Jain points out, the RoDTEP policy has a significant impact on Indian pharma's export performance. The Government has planned an increase in exports to $400 billion by the end of the financial year from the current level of $300 billion, which would make it an increase from 10 per cent to 15 per cent of GDP by the end of the decade.

Pharma will play an important role in the growth journey, explains Jain, with pharma exports expected to grow from $24 billion to $29 billion this year and to $75 billion by the end of the decade. But to achieve this, “All-round policy support will be important to harness the potential of the industry in the highly competitive and changing global landscape,” says the IPA chief.

India Pharma/Vaccine Inc, like its global peers, is looking at the COVID pandemic as both an opportunity to meet an unmet medical need as well as claim a slice of the COVID pie and gain market share. This is to be expected, after all, these companies have to also answer to their shareholders.

And the government too would like to prove India’s prowess in vaccine development with exports to countries that do not have this infrastructure yet. In fact, NK Arora, Chairman of the National Technical Advisory Group on Immunization in India has clarified that exports of COVID-19 vaccines from India will resume in 2022, once all adult Indians are fully vaccinated.

This is going to be a multi-year battle against the coronavirus, which requires both industry and government to align together. Thus the pharma sector might have to forgo the benefits of the RoDTEP scheme, keeping in mind the larger picture.

VIVEKA ROYCHOWDHURY Editor viveka.r@expressindia.com viveka.roy3@gmail.com

MARKET I N T E R V I E W

Inter-changeable designation for Semglee in the US is a milestone achievement for Biocon Biologics Dr Arun Chandavarkar, Managing Director, Biocon Biologics talks to Akanki Sharma about his role and vision for the company, while also throwing light on the future growth plans

In early 2021, you were appointed as the Managing Director of Biocon Biologics.

Tell us about your role and the vision that you have for the company.

Biocon has been a pioneer in the biosimilars sector having recognised the need to improve access for these critical biopharmaceuticals almost 20 years ago. It was subsequently carved out as a distinct subsidiary of Biocon to ensure a strong focus on this sunrise sector. My vision for the company is for it to be a global provider of quality biological products as affordable alternatives for the treatment of many critical diseases such as cancer, diabetes and autoimmune disorders. Further, my role would be to leverage our early successes, robust business fundamentals, technical excellence, highquality operations and broad product portfolio to deliver on our vision while evaluating new opportunities to serve patients.

Share a brief with us about Semglee - its R&D, manufacturing, the cost involved, benefits, etc.

Insulin glargine is a long acting basal insulin analogue that offers glucose control with the convenience of a once-daily injection and reduces the possibility of developing hypoglycaemia. It is prescribed for adults with type-II diabetes as well as adults and paediatric patients (children aged two years and older) with type-I diabetes.

Biocon Biologics has used its proprietary yeast platform based on Pichia pastoris to make recombinant human

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The investments in manufacturing infrastructure and R&D to support our insulins franchise runs into several hundred million dollars. It typically costs over a $100 million cumulatively to develop a biosimilar for the US, EU, Japan and other global markets insulin (rh-insulin) and its portfolio of insulin analogues like glargine and aspart. We have large-scale drug

substance and drug product manufacturing facilities in India and Malaysia and provide our insulin products in vials,

cartridges and disposable pen formats. We launched our biosimilar insulin glargine (Basalog) in India in 2009 after having launched our rh-insulin (Insugen) in 2004. In 2016, our insulin glargine became the first biosimilar from India to be approved and launched in Japan. We have been supplying our insulins (including glargine) to many other countries as well. We entered into a partnership with Mylan (now Viatris) for our insulin analogues in 2013 and through this collaboration received regulatory approval for insulin glargine (Semglee) in the USA in 2020. Our partner has also commercialised glargine in Europe in 2018.

In July 2021, our biosimilar insulin glargine received a historic US approval as the first inter-changeable biosimilar under the 351(k) regulatory pathway. We believe this inter-changeable designation for our glargine is a game-changing development, as it will allow pharmacy-level substitution of the reference product by our biosimilar, thus providing a convenient and affordable alternative. The USFDA decision validates Biocon Biologics' scientific, quality, clinical and regulatory excellence.

The investments in manufacturing infrastructure and R&D to support our insulins franchise runs into several hundred million dollars. It typically costs over a $100 million cumulatively to develop a biosimilar for the US, EU, Japan and other global markets.

What are the reasons behind

choosing Viatris as your partner for this product?

We have had a long standing partnership with Mylan (now Viatris) dating back to 2009 when we collaborated on developing biosimilar monoclonal antibodies and pegfilgrastim. This partnership leverages our complementary capabilities and is aligned to our common vision of enabling affordable access. We extended our collaboration further to include insulin analogues in 2013.

Viatris commercialises our codeveloped insulin glargine as Semglee.

Our collaboration includes one of the most extensive and diverse biosimilars portfolios globally and our partnership has been successful with five molecules from our joint portfolio approved in EU and other markets and three launched in the US. From a branding perspective, what's your strategy to ramp up Semglee's sales? Any plans to take it to other geographies?

If yes, let us know about the same. If not, why?

Viatris is responsible for commercialisation of our codeveloped glargine, Semglee, in the US, and it will be launching the product with an interchangeable label by end of the year. We believe substitution at the pharmacy counter will help broaden access to this important diabetes medicine for patients. Viatris is eligible for a 12-month exclusivity before the US FDA can approve another interchangeable biosimilar glargine.

Our insulin glargine is already

available in developed markets like Europe and Australia.

Biocon Biologics has also commercialised biosimilar insulin glargine in many markets like Japan, India, Mexico, Malaysia, Algeria, the UAE, South Korea, etc.

Tell us about three opportunities that you are looking forward to at Biocon Biologics.

In the next few years, we expect to see a higher growth on the back of key regulatory approvals and partnerships, both from expansion of the footprint of our existing portfolio to developed and emerging markets and introduction of new products.

The inter-changeable designation for Semglee in the US is a milestone achievement for Biocon Biologics in making insulin-based therapy accessible for people with diabetes globally. Commercial preparations for relaunch by the end of the year are underway.

While the European Commission has approved our biosimilar Bevacizumab and insulin aspart developed in partnership with Viatris, we await approval for these products in the US. These approvals were delayed on account of the COVID-related travel restrictions that prevented inspections of our manufacturing facilities in India and Malaysia. These approvals give us a robust portfolio of five biosimilars in the developed markets along with an economic interest in two more approved products in-licensed by Viatris from third parties.

Biocon Biologics already supplies recombinant human insulin for the benefit of diabetic patients in many emerging markets and we are now developing the product for the US based on the 351(k) biosimilar regulatory pathway.

Once approved, we would have basal, regular, mixed and rapid acting insulins for the benefit of people with diabetes in the U.S. What's next in the pipeline?

Is the company planning to come up with any other 'first-

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of-its-kind' product soon?

We continue to have a broad and robust pipeline of biosimilars that target market opportunities over the next ten years. Furthermore, we have recently partnered with the US-based Adagio Therapeutics to bring a novel

monoclonal antibody for the prevention and treatment of COVID-19, to patients in India and select emerging markets.

This "in-development" antibody treatment is being developed to cover SARS-CoV2 virus and its variants. It is now in phase-II/III trials and

an Emergency Use Authorisation (EUA) from the US FDA will be sought early next year.

This treatment potentially offers a convenient outpatient administration as a single intra-muscular injection for both prevention and treatment

of COVID-19. It has also been engineered to have a long halflife, potentially allowing for immediate and durable protection against COVID-19 for up to one year. akanki.sharma@expressindia.com journoakanki@gmail.com

EVENTS POST EVENT

DISSO INDIA2021 ONLINE

Tracking advancements in dissolution science and its applications The international conference of Society for Pharmaceutical Dissolution Science (SPDS) was conducted online in collaboration with AAPS, US on the theme, 'Dissolution as a Pivotal Tool for Drug Product Performance'

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he tenth annual international conference on Dissolution Science and Applications was held from June 24-26, 2021.

Conducted every year, the flagship conference by The Society for Pharmaceutical Dissolution Science (SPDS) is attended by pharmaceutical R&D, QA, QC & Regulatory as well as academia profes-

sionals from India and abroad, involving speakers from the US, Europe and Asia. This year, due to the COVID-19 pandemic, the international conference was conducted online in collaboration with AAPS, US. The theme of the event was "Dissolution as a Pivotal Tool for Drug Product Performance".

The event was supported

by companies like Sotax and ACG who were the Platinum partners of the event as well as Electrolab, USP, Mettler Toledo, Image Provision Technology, Inveniolife, Labindia, Cytiva, Agilent, Waters and Spookfish Innovation.

Disso India- 2021 Online had a total of 19 lectures from eminent professionals work-

ing in the pharma industry from around the world as well as academia coupled with a panel discussion. The subject experts presented various advances and developments related to dissolution science and its applications.

A highlight of this year's Disso India 2021 was sponsorship of the leading professional organization AAPS of

USA. Leadership of AAPS participated in the Disso India 2021 and shared their thoughts on the collaboration and scientific developments in the area of drug discovery, repurposing and human health.

Excerpts from the views and insights shared by the subject experts and leaders who attended Disso 2021.

It is important to understand and align on shared values between collaborating organisations On collaborations

It is easier to work with an organisation where the code of conduct and ethics is closely aligned with your own

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n my experience, collaborations turn out to be most fruitful if collaborators not only have an initial idea of shared interest and potential goals but also take the time to develop a framework and boundary conditions for the work, as well as up-front agreement on how outcomes are managed: both the successes and the challenges this will prevent "scope creep" as well as potential conflict over risks or who gets credit for what. It is also important to understand and align ahead of time on shared values between collaborating organisations: it is easier to work with an organisation where the code of conduct and ethics is closely aligned with

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your own. This again provides protection against potential conflicts and associated risks.

On repurposing medicines

Dr Tina Morris, Executive Director - American Association of Pharmaceutical Scientists (AAPS)

I can mostly speak on this from the quality and CMC perspective, but great challenges already exist in the clinical space and to demonstrate safety and efficacy for the new

indication(s) with medicines that were approved some time back with undoubtedly different clinical models or approaches.

In the CMC and quality space, "opening" an old drug to new applications draws the need for post-approval changes and with that the potential for quite extensive additional work to amend existing filings.

Ahigh degree of mistrust in healthcare systems are impacting decisions that patients make Main challenges faced by human health

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n my opinion, one of the main challenges faced by human health are a variety of social determinations of health (e.g., healthcare equity); specifically making healthcare accessible to all. I also think there is a high degree of mistrust in health care systems that are impacting decisions made by patients. They are not always in the best interest of the patient's welfare.

Rapid regulatory approvals becoming a norm in future The last four years have had strong FDA approvals (>45 approvals) with 2020 having 53 approvals (2nd highest in 20 years). In 2020, those products

Andy Vick, Regional General Manager & CVP, Safety Assessment Midwest, AAPS President

spanned 14 therapeutic areas, 40 per cent of those products were "first in class" products, 58 per cent of the approved drugs were in support of rare and orphan diseases and a high number of those were fasttracked or designated as breakthrough therapies. I believe these trends will continue and lead to a marked period of innovation in the pharmaceutical industry.

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EVENTS Material properties of the medicines and formulation strategies are critical for achieving their optimal dissolution and performance. One session was dedicated to these aspects and covered the following important topics:

Determination of bioequivalence is the biggest barrier towards development of topical and ophthalmic generic drug products Challenges in developing generic products for topical and ophthalmic products

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generic drug product is a copy of a reference drug product and is chemically identical to its branded counterpart. The generic drug product is pharmaceutically equivalent and bioequivalent and is therapeutically equivalent to brand name product.

Determination of bioequivalence is the biggest barrier towards the development of

topical and ophthalmic generic drug products.

USFDA initiatives to accelerate entry of topical generics into the market The FDA is conducting and sponsoring research to develop and identify in vitro and in vivo methods to determine the bioequivalence of topical drug products.

The research includes: ◆ Assessing new analytical

Dr Vinod P Shah, Pharmaceutical Consultant, North Potomac, MD USA

methods for characterising complex formulations ◆ Developing in vitro release testing methods and exploring in vitro-in vivo correlations ◆ Developing in vivo bioequivalence methods using open flow micro-perfusion and dermal microdialysis ◆ Skin pharmacokinetic methodology for topical drugs using non-invasive techniques such as Raman microscopy ◆ Developing in vitro bioe-

quivalence methodology ◆ Developing modelling and simulation methods to support in vitro bioequivalence evaluation (PBPK Modeling) FDA is regularly publishing Product-Specific Guidances to help the industry develop generic drug products. In addition, FDA has established "Center for Research on Complex Generics" to help in developing and educating stakeholders in the area of complex generics.

Advances in crystal engineering have fueled interest in cocrystals as novel materials for pharma development Role of cocrystals in drug development

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oor aqueous solubility is a significant challenge for the pharma industry. About 40 per cent of marketed drugs and 70-90 per cent of the drugs in the development pipeline have low water solubility. Solid-state modification and alternate solid forms are an important tool for enhancing aqueous solubility. Traditionally, metastable polymorphs, salt formation and amorphous form are used for solubility improvement. Salt form is applicable only for ionisable drugs while amorphous form, being a high-energy form it poses stability risks.

Cocrystals defined, as solids are crystalline single-phase materials composed of two or more different molecular and/or ionic compounds generally in a stoichiometric ratio, which are neither solvates nor simple salts. They have emerged as an alternate tool for non-ionizable drugs. Being

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crystalline cocrystals are less prone to stability risks. Pharmaceutical companies have embedded cocrystals in drug discovery programs, during the selection of optimal solid form. This has broadened the choice of solid forms for drug development. Advances in the area of crystal engineering, types of coformers and regulatory framework, have fueled interest in cocrystals as novel materials for pharmaceutical development. An increasing understanding of crystals structure-property relationship, allows engineering of supramolecular structure to attain desired material properties.

Challenges of using cocrystals for product development Using cocrystals as a drug substance for product development offers challenges, due to their structural features and unique properties.

Cocrystals are a multi-crys-

Pharmaceutical companies have embedded cocrystals in drug discovery programs, during the selection of optimal solid form Arvind Kumar Bansal, Professor and Head, Department of Pharmaceutics, NIPER S.A.S. Nagar

talline solid form that produces super-saturation.

Hence, it is important that solubility advantage be maintained for a biopharmaceutically relevant time period, to

obtain bioavailability advantage. Solution mediated phase transformation (SMTP) converts the cocrystals to the parent drug, thus nullifying solubility advantage.

Formulation interventions involving the use of polymers and surfactants, can modulate SMTP, and provide prolonged

super-saturation. Additionally, it is challenging that while optimising solubility, other physic-chemical/mechanical properties like chemical stability, hygroscopicity and compaction may also change. This makes it mandatory to screen the optimal cocrystal candidate, using comprehensive preformulation profiling. Latter involves evaluating essential properties (solubility, dissolution, permeability, stability and hygroscopicity) and desirable properties (polymorph screening, mechanical properties, excipient compatibility studies). This helps in identifying development risks and designing mitigation strategies.

Adopting a tiered approach of (i) selection of cocrystal candidate, (ii) rational formulation and process design, and (iii) container closure system, can help in achieving a robust cocrystal based product.

EVENTS

More and more scientists will opt for Apparent Dissolution rather than Intrinsic Dissolution Role of intrinsic dissolution in characterising the quality of APIs

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nlike conventional dissolution studies performed using USP Apparatus, I to VII, Intrinsic dissolution is performed on the API as such i.e. without adding anything else like the excipients of the formulation to it. So it truly reflects on its intrinsic/inherent properties like its solubility, dissolution rate, BCS class,

USP, Type I or Type II apparatus. So there is no need for any different apparatus per se.

However based on the feedback received from users, Apparent Dissolution which is of-

ficial in EP 2.9.29, is far superior as compared to Intrinsic dissolution USP <1087>. This makes the use of API as such without any compaction. USP Apparatus 4 (flow-through

cell) is used for this purpose.

There are several advantages like a more realistic picture of solubility characteristics, faster release, no issue of sink condition control, no possibil-

ity of changes in the crystallinity due to compaction etc.

I personally feel that more and more scientists will opt for Apparent Dissolution rather than Intrinsic Dissolution.

Vijay Kshirsagar, Director-TRAC Pharma Consulting, President-SPDS

comparative solubility study of different morphs or the salts and different particle sizes of the same molecule and its solvates too. You have the choice of using a rotating or stationary disc for the compacted mass of the API. So it helps to have a complete understanding of the important properties of API, described above.

This has become more important now as most of the new chemical entities are insoluble. So it is a challenge for the formulator to ensure that product developed shall see the light of the success in BA/BE studies. The proper characterisation is going to help in this task.

Dissolution set up suited for determining intrinsic dissolution Intrinsic dissolution set-up just needs a special disc holder which can be fitted into any

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www.lubrizol.com/Health

EVENTS

Particle morphologyis an important parameter when it comes to qualityand performance of drug dissolution Role of particle morphology in drug dissolution ◆ Particle morphology is an important parameter when it comes to the quality and performance of the drug dissolution. ◆ Particle morphology along with particle size is an important attribute in APIs, solid oral drug products (tablets and capsules - impacting on homogeneity, flow and processing), and as a critical quality attribute in semi-solids (suspensions) and sterile liquid products (injectables). ◆ The rate of drug dissolution is directly proportional to the surface area of the particle.

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Particle morphology has a direct impact on the surface area. Hence, particle morphology plays an important role in drug dissolution.

Tools available to characterise particle characteristics including morphology, to help in interpretation of dissolution data There are different methods available such as particle analysis technology including microscopy method, spectroscopy, laser scattering and solid-state characterisation techniques to determine particle properties.

Sandeep Kulkarni, Scientific Director, Image Provision Technology, India

Whenever we try to study the correlation of physical properties of particles on dissolution data, the major parameters are particle size and particle morphology. The popular technique for particle size analysis is Laser Diffraction technique. Since Laser Diffraction gives only particle size, most of the dissolution profiling studies are done in correlation with Particle Size. But the research says particle shape (morphology) plays a bigger role while studying the role of physical properties of particles on dissolution.

Microscopic particle size and shape systems are used to

get particle morphology data.

The quick and accurate method allows researchers to quickly correlate the dissolution data with particle morphology. Particle morphology helps in interpreting the dissolution profiles of different samples more judiciously and give a better understanding of correlation.

More advanced systems of automatic microscopic size and shape analysis data with Machine Learning and Artificial Intelligence gives an in-depth understanding of particle morphology and gives details about every particle of the sample.

The data proves very useful in Dissolution Studies.

EVENTS Novel drug delivery systems offer a unique challenge for conducting meaningful dissolution. Custom made dissolution methodologies help in performing dissolution testing of these sophisticated products.

Nanocarriers offer similar challenges during dissolution,be it SNEDDS,liposomes,SLN or polymeric nanoparticles Selection of best dissolution method for a nanocarrier-based system

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issolution methods for nanocarrier based systems need to address the critical aspect of nanocarrier size, a unique feature that differentiates nanocarrier based systems from other systems. Accordingly, there are two basic options. The sample and separate method and the dialysis sac or membrane methods. In the first method separation of the nanoparticles from the sample aliquot is the major challenge.

Further, this method is generally relied on only when the use of a dialysis membrane poses constraints.

The dialysis methods are gaining popularity and acceptance. Nevertheless, it is important to ensure that the method provides good reproducibility, is discriminating and is easy to handle. Our experience in working on USP I, USP II and USP IV proposes the USP IV or flow-through cell apparatus, with a ready to use dialysis adapter (Floatalyzer) as a practical method for nanocarrier based systems.

Recommendations for developing a dissolution method for SNEDDS Nanocarriers generally offer similar challenges during dissolution, be it SNEDDS, liposomes, SLN, polymeric

Prof Padma V Devarajan, Dean, Research and Innovation, Professor in Pharmacy and former Head, Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai

nanoparticles etc. This challenge is generally related to

their size. Nevertheless, lipidbased formulations like

SNEDDS and SMEDDS due to the lipidic contents could affect the permeability of the dialysis membrane to create artefacts. One approach is to dilute the formulation as much as possible for the dissolution test, to minimise such effects.

Another option is to use a dialysis membrane with a molecular weight cutoff much greater than the suggested 10 fold cut off. If both options are not found effective one must rely on the sample and separate method, with an effective approach for separation which could be ultracentrifugation, syringe filtration through appropriate filters, ultrafiltration or maybe even pressure filtration.

When developing generic products,it is of utmost importance to identifythe Critical QualityAttributes Role of USP type IV in accelerated development of generic products

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major advantage of the flow-through cell dissolution method sits in its versatility. When developing generic products, it is of utmost importance to identify the Critical Quality Attributes (CQA).

Indeed, a generic product should demonstrate bioequivalence with the Reference Listed Drug (RLD) product.

Depending on its biopharmaceutical class (as per US FDA BCS), failures may occur which may be due to either the active ingredient or the formulation.

The flow-through cell, used with different approaches, may bring a lot of knowledge about the relative importance of each CQA. Apparent dissolution may allow to compare different

sources or active ingredients and to determine the critical attributes (for example particle size).

From a different perspective, the different hydrodynamics provided by the flowthrough cell allows achieving very different discrimination properties, in comparison to conventional paddle and baskets.

Gathering all that product knowledge from the early stages of product development facilitates successfully completing the development cycles, with no or limited failures.

Thus, avoiding losing time due to generic development failures.

Products best suited for USP type IV apparatus Another important advantage of the flow-through cell disso-

The different hydrodynamics provided by the flow-through cell allows achieving very different discrimination properties, in comparison to conventional paddle and baskets

Samir Haddouchi, Managing Director, SPS Pharma Services

lution method is its flexibility.

For example, it is possible to make a dissolution test with 50 mL of medium or with 50 litres, depending on the

solubility of your active ingredient and the dosage strength of your formulation.

It is possible to have short dissolution tests running for one hour only but bringing good discrimination compared to the paddle method or very long tests running for days, weeks or months for long-acting products such as implants or injections.

Moreover, some specific applications were developed over the past years for challenging products such as lipid-based products (suppositories, soft gelatin capsules, etc…)

Overall, there is no product that is best suited for flowthrough cell methods because that method can accommodate almost all types of dosage forms.

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EVENTS Advancements in the area of dissolution methodologies are improving the quality of the data and outcome from the experiments. Coupled with advancements in the area of instrumentation like automation, they are fueling the emerging trends in dissolution testing. Another important but under-researched area in dissolution science is the hydrodynamics of medium during dissolution testing. Following are some of the thoughts shared during Disso India 2021 regarding the developments in the area of dissolution - methodologies, instrumentation and hydrodynamics

Use of dynamic dissolution methods is likelyto be spurred on by recentlypublished FDAdraft guidance Current status of dynamic dissolution in various pharma companies

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any companies are using dynamic dissolution methods as biopredictive tools.

There are a wide range of dynamic dissolution approaches available and range from simple transfer methods such as the gastric to intestinal media switch method developed during the IMI OrBiTo programme to more automated systems such as the Artificial Stomach Duodenum model, Gastrointestinal Simulator and Bio-GIT. For some projects, accounting for permeability is an important aspect to incorporate in dynamic dissolution method design and biphasic systems which utilise an organic layer to provide a sink for a dissolved compound can be used, a commercial example of equipment that provides this capability is the Pion Inform platform.

Other approaches can be used

to achieve separation of dissolved drug substance and range from membrane-based systems such as the In Vitro Dissolution Absorption System (IDAS) system from Absorption Systems to cell monolayers in the Dissolution-Permeation system from Prof. Shinji Yamashita's lab in Setsunan University, Japan. More complex dynamic dissolution models such as the Physiolution dissolution stress-test device or the Gastroduo equipment from the University of Greifswald (Germany) can be used to assess the impact of gastric conditions and/or physical flow effects on dosage form performance. At Pfizer, we have access to the TIM-1 gastrointestinal simulator which we use to profile the performance of oral dosage forms under simulated clinical dosing conditions including fasted, fed and achlorhydric states. We use this tool to derisk formulation changes dur-

ses' which stresses the importance of establishing an in vitro - in vivo link to support clinically relevant drug product specifications and encourages exploration and development of new approaches to link pharmaceutical quality aspects with clinical performance.

Dr Mark McAllister, Senior Scientific Director in the Drug Product Design group, Pfizer (Sandwich)

Combining dynamic dissolution with other concepts like biorelevant dissolution media, to provide inputs for computer modellings like PBAM and PBBM

ing development and it can also be used to assess the performance of formulation variants to support the development of dissolution specifications. The use of dynamic dissolution methods is likely to be spurred on by the recently published FDA draft guidance (September 2020) on 'The Use of Physiologically Based Pharmacokinetic Analy-

Integration of dissolution data from dynamic methods with PBAM/PBBM to better inform predictions of oral dosage form performance is an area of active research interest, for academic, industrial and regulatory scientists. While PBAM/PBBM approaches are very useful tools to guide oral drug product development, their capabilities are often limited by input pa-

rameters that are more directly related to the physicochemical properties of the active pharmaceutical ingredient (API) than the performance of the formulated drug product. For example, capturing the impact of excipient changes such as a switch to a different particle size grade of filler or evaluating the impact of process changes, such as increased lubrication, are difficult to do directly using the direct inputs to the typical software used to perform PBAM/PBBM. Ideally, we would use input datasets that describe drug dissolution in dynamic biorelevant conditions comparable to those observed in the gastrointestinal tract to improve the prediction of drug product performance using PBAM/PBBM. Effective coupling of in vitro and in silico approaches would improve the likelihood of robust and accurate predictions of product performance.

Biopredictive dissolution testing can be used to rank-order formulations in terms of in vivo performance Importance of biopredictive dissolution

B

iopredictive dissolution testing is important because it has the potential to enable the development and selection of formulations that perform well in the population of interest and decrease the need for reformulation or multiple pre-clinical or clinical studies. When designed with the target population in mind, biopredictive dissolution testing can be used to rank-order formulations in terms of in vivo performance, and also begin

20 EXPRESS PHARMA September 2021

to assess the sensitivity of the formulations to gastrointestinal variables.

A main challenge in the development of biopredictive dissolution for poorly soluble drugs is related to gastrointestinal conditions

Challenges in the development of biopredictive dissolution One of the main challenges in the development of biopredictive dissolution for poorly soluble drugs is related to gastrointestinal conditions, for example, the impact of fluid hydrodynamics and mixing (e.g. shear rates) on dissolution rate. While biorelevant dissolution media have

Deanna Mudie, Principal Scientist, R&D, Lonza, Bend, OR, US

evolved with our understanding of gastrointestinal physiology and cover a wide range of in vivo relevant properties and compositions, establishing a link between

shear rates in vivo and shear rates in commonly used dissolution apparatuses and impacts on drug performance is less straightforward.

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Biorelevant models that evaluate solubilityand permeability simultaneouslycan improve prediction of product performance Permeability and solubility provide critical information for product development

I

n order for an administered drug to be absorbed, two upfront processes must occur; the formulated product must dissolve and the released drug must go into solution. At that point, permeability comes into play and becomes the final determining factor in how much of the dose will be absorbed. While data from in vitro solubility and dissolution experiments could help predict oral absorption by theoretical calculations several challenges remain due to the fact that absorption is affected by other factors including but not

limited to the physiological conditions of the GI tract, food effects, the effect of formulation etc. Dissolution, solubility and permeability are typically measured independently and their measurement is done under conditions that may have less physiologic relevance. Formulation strategies can help improve the apparent solubility of the drug, however, the concomitant evaluation of permeability under physiologically relevant conditions is necessary to understand the interplay between solubility and permeability and the impact of one on the other. Biorelevant models which can evaluate solubility and permeability simulta-

Developments in instrumentation for obtaining solubility and permeability data

Vatsala Naageshwaran, Chief Business Officer, Absorption Systems, USA

neously within the same system can therefore improve the prediction of product performance.

In Vitro Dissolution Absorption System (IDAS) is an instrument that is designed for the simultaneous evaluation of drug dissolution and permeation, especially for drugs that are poorly watersoluble in vitro. It comprises two compartments, donor and receiver, which are separated by a vertically mounted biorelevant membrane. The donor compartment of IDAS which represents a standard dissolution chamber contains simulated intestinal fluid in the fed or fasted state, while the receiver compartment contains pH 7.4 transporter buffer contain-

ing four per cent BSA to represent human plasma and help maintain sink conditions. Samples are withdrawn from the donor and receiver chambers at various time points and analysed

by LC-MS/MS in order to visualise both dissolution/solubility and permeability/absorption concomitantly. This system can be effectively utilised to characterise food effect using fasted or fed intestinal fluids, BCS Classification of compounds, formulation modifications such as particle size changes (nano vs micro), viscosity, supersaturation for weakly basic drugs with low solubility and interactions with transporters.

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PBBM provides opportunityto accelerate drug product development, gain regulatoryflexibilityand ensure patient-centric drug product quality Historical development in the field of PBBM

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hysiologically-based pharmacokinetic (PBPK) modelling has been successfully applied over the last decade to predict first in human drug exposure, assist with formulation selection and support clinical pharmacology applications such as estimating the dose in special populations and evaluating potential drugdrug interactions, with the ultimate goal of supporting regulatory decision making.

However, the typical inputs for current PBPK models only account for rudimentary properties of the formulation, thus requiring further refinement as it is applied to support biowaivers for formulation, manufacturing and/or control changes (refer in here as CMC changes). Physiologically-based biopharmaceutics modelling (PBBM) is a modelling approach recently created from the scientific debates that occurred at two FDA sponsored workshops which focused on topics related to the application and gaps in knowledge of emerging tools, such as physiologically-based modelling in support of drug product quality1,2.

To this, PBBM emphasises the role of biopharmaceutics modelling combined with PBPK modelling to facilitate the establishment of the essential in vitro (e.g., dissolution)/in vivo (systemic exposure) link needed to: 1) Enhance drug product understanding, 2) Ensure patient-centric drug product quality and 3) Gain regulatory flexibility e.g., reduce the need for in vivo data to support regulatory assessment.

PBBM shares some common steps with PBPK modelling, such as building the disposition and absorption models and their verification

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using the appropriate data.

However, the main purpose of PBBM is to provide a mechanistic understating of in vivo drug release, with an emphasis on the effect of CMC changes. This is contrary to PBPK modelling where, in many cases, the drug absorption rate constant is fixed or characterised based on some general factors. Another key difference between PBBM and PBPK modelling is that to evaluate the in vivo impact of CMC changes, a safe space needs to be built using either an in vitro in vivo relationship (IVIVR) or in vitro in vivo correlation (IVIVC).

Thus, with PBBM, one must have dissolution data as an input. Since the main focus of PBBM and PBPK modelling are different (just like the focus of biopharmaceutics and clinical pharmacology are different), it is important to have a separate terminology to not only differentiate their appli-

Sandra Suarez-Sharp, Simulations Plus

creased over the last thirty years, from approximately $150 million in 1970 to about $2.6 billion in the last decade, and this is in part due to the rising cost of clinical trials and associated processes 3.

duce the number of studies needed to accelerate drug product development and thus, decrease the cost of medicines.

Compared to conventional modelling approaches, PBBM can guide the development of a biopredictive dissolution method early in drug product development by leveraging the scientific community's knowledge and experience through pooling physicochemical data, in vitro characterisation, preclinical and clinical data. PBBM can also accelerate compound identification and formulation selection (e.g., going from IR to ER) by decreasing the number of trial-and-error studies. Because a well-established and validated PBBM model can contribute to enhanced product understanding and help close the gap between in vitro testing and in vivo performance, it is likely that PBBM will increase the likelihood of

The implementation of PBBM provides an opportunity to take a major step not only in accelerating drug product development but also in gaining regulatory flexibility and ensuring patient-centric drug product quality. Building confidence with this approach is essential and a stepping stone toward regulatory policy cations, expectations in terms of data needed, and additional validation steps but to also encourage the advancement of physiologically based modelling to support drug product quality applications.

Role of PBBM in accelerating drug product development and gaining regulatory flexibility Drug development costs and time have exponentially in-

This alarming increase in the cost of pharmaceuticals constitutes a burden to the healthcare system and the patients, especially the elderly.

Regulatory agencies such as the FDA believe that the implementation of model integrated drug development 4 (i.e., the combination of models and data) will likely result in higher confidence in the efficacy and safety of the drug product sooner in development. This, in turn, may re-

establishing a safe space via IVIVRs/IVIVCs, supporting drug product quality-related biowaivers.

In addition, PBBM has been used in a variety of biopharmaceutics justifications for regulatory decision making for both ANDA and NDA submissions, including: 1. The extension of biowaivers from the Biopharmaceutical Classification System (BCS) beyond BCS I/III

substances containing drug products.

2. As supportive information for additional drug product strength biowaivers.

3. The establishment of bioequivalence for locally acting drug products, specifically in the identification of clinically relevant bioequivalence measures.

4. To ensure therapeutic equivalence across patient populations or special conditions without additional studies.

5. To support the establishment of clinically relevant drug product specifications, determination of critical quality attributes, or evaluation of risks associated with changes in release rate.

The implementation of PBBM provides an opportunity to take a major step not only in accelerating drug product development but also in gaining regulatory flexibility and ensuring patientcentric drug product quality.

Building confidence with this approach is essential and a stepping stone toward regulatory policy.

References [1]. Suarez-Sharp S, et al.

Applications of Clinically Relevant Dissolution Testing: Workshop Summary Report.

November 2018. The AAPS Journal 20(6); DOI:10.1208/s12248-0180252-3 [2]. Pepin XJH, et al. Current State and Future Expectations of Translational Modeling Strategies to Support Drug Product Development, Manufacturing Changes and Controls: A Workshop Summary Report. J Pharm Sci. 2021 [3]https://www.reutersevents.c om/pharma/column/searchpharmas-moores-law [4]. https://www.fda.gov/ drugs/regulatory-scienceaction/impact-story-modelingtools-could-modernize-genericdrug-development

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Automation in UV/VIS spectroscopyaugments various aspects in analytical measurement Advantages of automated spectroscopic measurement

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utomation in UV/VIS spectroscopy augments various aspects in analytical measurement. Most of them cover efficiency and effectiveness thanks to the unattended operation, workflow compliance, security and optimisation, which at the end improve time-to-result significantly. If the automation system is well qualified to the requirements, the ROI including maintenance of the investment is usually achieved within one year.

Challenges of combining automated spect roscopic measurement with dissolution apparatus If the dissolution system including the integrated spectrometer is scalable, modular and regulation-compliant, all aspects of the automated sample journey encompassing sample preparation, measurement and throughput can be optimised to a maximum extent. Whenever required or enforced by the analytical workflow, the spectrometer can be automatically qualified with CRM changing devices

If the automation system is well qualified to the requirements, the ROI including maintenance of the investment is usually achieved within one year

Dr Hans-Joachim Muhr, Head of Strategic Product Group UV/VIS, Mettler-Toledo GmbH, Analytical, Switzerland

prior to any dissolution testing run. Especially the data-integrity according to FDA and ALCOA+ regulations require seamless integration of a

UV/VIS spectrophotometer into the dissolution system by providing the appropriate interface and respective validation expertise.

There are multiple hydrodynamic effects that need to be considered in pharma dissolution testing Role of hydrodynamics in the dissolution of a sample

T

his is an interesting question. Probably, the first thing that springs to mind when one considers hydrodynamics and dissolution, is that the velocity, or agitation, of the dissolution medium, can affect the thickness of the diffusion boundary layer.

In other words, greater agitation will lead to a reduced boundary layer thickness and an increased dissolution rate. However, there are multiple hydrodynamic effects that need to be considered in pharmaceutical dissolution testing. How will hydrodynamics affect a mass of particulates, for example after tablet disintegration? Will a change in local hydrodynamics lead to better particle dispersal, which could increase the exposed surface area and thus increase dissolution also through a surface area effect? A typical example of this is when the paddle apparatus agitation rate is increased with a view to mitigating coning effects -hydrodynamics in this case aren't acting (solely) on dissolu-

tion via boundary layer thickness, but also via particle dispersion effects. In a similar vein, the effects on particle motion and relative fluid velocity need to be considered - are the hydrodynamics sufficient to suspend a particle or will it remain sedimented at the base of the dissolution vessel/cell? How will increasing or decreasing fluid velocity impact the relative velocity (the difference between particle and fluid velocity) if the particle is moving with the fluid?

In some scenarios, increasing fluid velocity might not notably impact the dissolution rate, if the particles are well dispersed and moving with the fluid for example. In other scenarios, increasing agitation might change the particle behaviour sufficiently to increase relative velocity and disperse particles.

Differences in hydrodynamics of various types of dissolution apparatus Each apparatus has its own hydrodynamic characteristics, and variations in apparatus setup

Each apparatus has its own hydrodynamic characteristics, and variations in apparatus setup can also affect the hydrodynamics

Dr Deirdre M. D'Arcy, Associate Professor in Pharmaceutics and Pharmaceutical Technology, School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin

can also affect the hydrodynamics. The paddle in the paddle apparatus is a more efficient stirrer than the basket of the basket apparatus, therefore higher velocities, in general, are present in the paddle apparatus at comparable rpm -though there is still a low-velocity region at the centre of the vessel base at

common operating speeds. The flow-through apparatus is usually used with a pulsing flow, therefore the velocities in the cell vary over the course of the pulse.

Furthermore, velocities can vary across the cell. It should always be remembered that for the same flow rate, the fluid velocity will be lower in the larger 22.6 mm diameter cell than the 12 mm diameter cell. Overall velocities are quite low in the flowthrough apparatus compared to the paddle or basket apparatus, but the positioning of the dosage form with respect to the new medium entering the cell is very different to the set-up in the paddle and basket apparatuses, so it is difficult to directly compare the effect of overall apparatus

velocities.

Therefore to provide a more comprehensive answer to this question, I would point the reader to a review we published in August 2017 in Dissolution Technologies (http://dissolutiontech.com) where we discussed the main hydrodynamic features in the basket, paddle and flowthrough apparatuses (Characterization and Simulation of Hydrodynamics in the Paddle, Basket and Flow-Through Dissolution Testing Apparatuses - A Review; Todaro et al., August 2017, dx.doi.org/10.14227/ DT240317P24).

There have also been more recent studies published on the basket apparatus hydrodynamics.

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Hydrodynamics in dissolution apparatus can be comprehensively studied using particle image velocimetry PIV suitability for studying hydrodynamics in dissolution apparatus

T

he hydrodynamics in dissolution apparatuses has been historically investigated by using both Experimental Fluid Dynamics (EFD) and Computational Fluid Dynamics (CFD) methods. While CFD simulations are typically less expensive compared to EFD methods, especially in relation to parametric studies, EFD methods provide real data and are usually necessary to validate at least baseline CFD models. In that way these two are complementary to each other. With regards to dissolution apparatuses, available literature indicates that many different EFD methods have been used including Particle Image

Velocimetry (PIV) for the study of associated hydrodynamics.

One of the advantages that PIV offers over some of the other EFD methods is that information can be obtained across various regions of interest (such as planes). This provides a comprehensive understanding of what happens all along the liquid domain and thus PIV can be successfully employed to understand hydrodynamics in dissolution apparatuses.

One of the advantages that PIV offers over some of the other EFD methods is that information can be obtained across various regions of interest (such as planes)

Modifications in future design of USP dissolution apparatus 1, based on principles of hydrodynamics The presented work focused solely on the characterization of hydrodynamics within Appara-

Dr Satish Perivilli, Senior Scientist II, Dosage Form Performance Laboratory USP, US

tus 1 by investigating velocity magnitudes at distinct areas of interest. Hydrodynamics is only one of the many factors that influence dissolution profiles obtained with dissolution apparatuses. The other important and inter-connected factors are the dosage form formulation, analytical method (i.e., test procedure), instrument setup, media properties etc. These factors all play a

role in the performance of any dosage form under different test conditions. To modify the design of any apparatus based on characterization of the hydrodynamics alone is, in my opinion, premature. A complete understanding of the apparatus requirements and overall performance would be required before any design modifications could be considered.

The dosage form (formulation) should drive the dissolution/release process and not the reverse Critical points of a dissolution method to predict performance of a dosage form

T

he prediction of the performance of the dosage form will drive the identification and determination of the critical points, thereby setting the experimental quest and strategy to accomplish the desired objective(s). These contexts could be - prediction of in vivo performance, attributes of the profile, setting QC specifications, discriminatory and/or sensitivity characterisation, and the like. In the broadest sense and in general, perhaps, the commonality with respect to the critical point(s) and the contexts is that the relation between the physicochemical properties of the active ingredient combined with the formulation characteristics (so-called technology) that drive the dissolution/release performance of the dosage form, i.e., func-

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tional characteristics, should be identified - they will provide the necessary critical considerations (points). The bottom line, the dosage form (formulation) should drive the dissolution/release process and not the reverse. This is a very involved topic that is not only multidisciplinary but also requires extensive analyses and discussion which will be drug and drug-product specific.

As the components of the formulation start to influence the process of dissolution of the active ingredient, the resulting dissolution profile is dependent, if not specific, on the components and the composition as well as the process, which is generally referred to as the 'technology'

Utilising dissolution data for patent protection The solubility of the solute (active ingredient) is a prerequisite for its dissolution from the dosage form that contains the solute. Given that a solute that is soluble in a solvent placed in that solvent will solubilise (dissolve). As a result, solubilisation and thereby its dissolution from a dosage form will be akin to its solubilisation provided the excipients do not interfere in the

Dr Umesh Banakar - Professor and President, Banakar Consulting Services, USA

process of dissolution of the drug from the formulation. As the components of the formulation start to influence the process of dissolution of the

active ingredient, the resulting dissolution profile is dependent, if not specific, on the components and the composition as well as the process, which is generally referred to as the 'technology'. Hence, the combination of the technology and the resulting

dissolution/release performance, often in specific dissolution/release tests (conditions) are assessed for patentability.

This is one of the simple ways in which the pharma industry explores dissolution/release data to secure patent protection.

cover )

India has huge vaccine manufacturing capabilities but ensuring strict adherence to Good Manufacturing Practices (GMP) will be crucial to build credibility in the safety and effectiveness of its vaccines for continued progress. India Vaccine Inc should ramp up its capabilities in terms of people, technology and processes to ensure top-notch standards in GMP and data documentation

By AKANKI SHARMA

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cover ) I

ndia was the largest (second if the European Union is considered as one component) vaccine-exporting country in the pre-pandemic period (specifically 2017-19).

Further, it is also home to the world's largest vaccine manufacturer - namely, the Serum Institute of India, which accounts for the production of more than 1.5 billion doses. The country exports vaccines (for polio, diphtheria, tetanus, pertussis, BCG, hepatitis B, measles, mumps, rubella, etc.) to more than 170 countries, and 65 per cent of the children worldwide have received at least one vaccine manufactured by the Serum Institute.

While the years 2020 and 2021 registered a reduction in the export of vaccines from India, it continues to be amongst the top five countries in the production of COVID-19 vaccines worldwide.

This being noted, India faced global regulatory blocks for its home-grown vaccine until April 2021-22. However, with the availability of additional trial data from April/May 2021 onwards, and published studies and research conducted by independent research centres (such as papers published by the Lancet, the Cambridge University Press and Dr Fauci's institute), the discomfiting scepticism has eased. Further, basis the representations by the Government of India, Covaxin manufactured by Bharat Biotech may be approved by the World Health Organization (WHO) for emergency use by the end of this month.

Thus, India has huge vaccine manufacturing capabilities but ensuring strict adherence to Good Manufacturing Practices (GMP) will be crucial to build credibility in the safety and effectiveness of its vaccines for continued progress.

So, what will this entail?

Let's learn from the industry experts Speaking about the existing standards of Good Manufactur-

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Vaccine hesitancy in India was fuelled by concerns over vaccine safety and scepticism about the efficacy of the Covaxin vaccine, which had been hurriedly approved before the completion of the phase-III clinical trials Sidharrth Shankar Partner J Sagar Associates

Validated decontamination measures should be available for each organism or group of related organisms. A campaign production strategy may be chosen based on a systematic risk management approach for each product, all this without compromising crosscontamination issues Sanjiv Navangul MD and CEO Bharat Serums and Vaccines

We must develop a robust communication strategy based on scientific pieces of evidence and engage with all the stakeholders globally to compete in an ethical manner and derail the well-designed propaganda against India-made pharmaceutical products Professor Bejon Kumar Misra Founder Director Patient Safety and Access Initiative of India Foundation

ing Practices (GMPs) for vaccines, Sidharrth Shankar, Partner, J Sagar Associates, says, "The Indian GMPs standards are covered primarily under Schedule M of the (Indian) Drugs & Cosmetics Act (D&C Act), which, inter alia, incorporates the spirit of WHO's GMPs in terms of quality controls, stability studies, etc. The extant regulatory framework

provides an extensive set of norms for quality assurance, self-inspection, and quality control system requirements, as also for clinical development of any vaccine, including the COVID-19 vaccines. In order to ensure quality drug formulation, manufacturers are required to comply with certain SOPs, detailed control systems, specifications, validation and

process requirements about location and surroundings; building/premises; waste disposal protocols; conduct of personnel on the premises; health, clothing and sanitation; recordkeeping protocols; etc."

He added, "Some of the major exigencies in ensuring strict adherence of current GMPs (cGMP) during all stages of the product lifestyle are lack of

proper training for the appointed employees that frequently leads to errors in maintenance of records and occurrence of contamination; inadequate protocols for quality assurance system and documentation management; and lack of awareness of the urgency for a comprehensive assessment of the manufacturing, processing and packaging of the facilities, final products and the systems in place."

The Indian government has issued draft regulatory guidelines for the development of vaccines with a focus on the COVID-19 vaccine, especially quality controls, and the continued requirement of compliance with GMP norms specified under the law. In terms of the draft guidelines, end-to-end control testing (including testing for process additives and process intermediates) is required to be demonstrated by the manufacturers of COVID-19 vaccines. Further, to ensure global compliance and strict quality assurance, and to bolster exports, the government is revisiting the current framework to bring it on par with the latest WHO-GMPs by incorporating extensive pharmaceutical quality systems, quality risk management, suppliers audit and approval requirements, he notifies.

According to Sanjiv Navangul, MD and CEO, Bharat Serums and Vaccines, GMP compliance take into account multiple factors right from a well-defined manufacturing process, a dedicated production facility, a finalised containment strategy as per biosafety levels, to having automated equipment with the least manual intervention from an employee safety perspective.

Keeping in mind the current scenario, he suggests, "All employees working in the manufacturing zone should be vaccinated with appropriate specific vaccines and periodic health checks."

He also emphasises that every company has to ensure the use of clean-in-place and sterilise-in-place systems. Even

the filtration of the exhaust is a process - filters need to be changed by employing bag-inbag-out housings and those have to be decontaminated and properly destroyed, once removed.

"Accidental spillages, especially of live organisms, must be dealt with quickly and safely.

Validated decontamination measures should be available for each organism or group of related organisms. A campaign production strategy may be chosen based on a systematic risk management approach for each product, all this without compromising cross-contamination issues," he adds.

Professor Bejon Kumar Misra, Founder Director, Patient Safety and Access Initiative of India Foundation, informs that the guiding principle of GMP is that quality is built into a product, and not just tested into a finished product. Therefore, the assurance is that the product not only meets the final specifications but that it has been made by the same procedures under the same conditions each and every time it is made. There are many ways this is controlled - controlling the quality of the facility and its systems, controlling the quality of the starting materials, controlling the quality of production at all stages, controlling the quality of the testing of the product, controlling the identity of materials by adequate labelling and segregation, controlling the quality of materials and product by adequate storage, etc. All of these controls must follow prescribed, formal and approved procedures, written as protocols, SOPs, or Master Formulae, describing all the tasks carried out in an entire manufacturing and control process.

Regarding the current gaps in ensuring cGMP, he says, "We do not have any gaps, except we are unable to convince the global community about our competence and capabilities."

Adding to it, Vinay K Mayer, Director - Market Research and Consulting, Asia Research

Pharma companies from the US and EU are looking at India as a potential market for generic drugs, especially vaccines. Efforts are being made by the Indian government to make vaccines affordable and accessible for the masses Vinay K Mayer Director - Market Research and Consulting Asia Research Partners

Lack of transparency creates avoidable buzz and suspicion. Over and above this, there has been no clear picture on the extent of ADRs caused because of the vaccine, or associated with it. At one level, this is also a problem worldwide because of the accelerated paradigm of emergency use authorisation and confounding pictures of the virus' variants S Srinivasan Managing Trustee Low Cost Standard Therapeutics (LOCOST) and co-Convenor, All India Drug Action Network (AIDAN)

Partners, says that throughout the pharma manufacturing and supply world, compliance to cGMP is often problematic because of data management system design. The guidelines stipulate that data manipulation needs to be guarded against, but some current systems designed for providing access to data also enable it unintentionally by design. The key differentiating factor between intent and behaviour depends on how extensive and rigorous quality oversight is throughout an organisation's internal processes - not through the false perception of end-of-arm devices or software.

Role of industry and policymakers Mayer informs that for closing the gaps in cGMP, management must be open about quality and cGMP compliance risks and

concerns, and the personnel must feel relaxed, safe, and able to openly communicate the risks and concerns so that they can be acknowledged, assessed, and addressed accordingly. A management response that "shoots the messenger" will widen the gap even more and leave the firm exposed to damaging non-compliance and regulatory citations. Moreover, understanding what is critical material within a specific procedure or area and working with a deeper knowledge of critical product attributes eventually leads to greater process control.

Professor Misra also suggests, "We must develop a robust communication strategy based on scientific pieces of evidence and engage with all the stakeholders globally to compete in an ethical manner and derail the well-designed

propaganda against Indiamade pharma products. The Ministry of Commerce and Industry should engage with patient organisations globally and create the demand for Indian vaccines, which are already popular. I have been saying this to the Pharmaceutical Export Promotion Council of India for several years but certain vested interest working against India is not allowing our intervention to take place globally in the interest of our country and global community. We shall continue our efforts to attract the attention of our Prime Minister to ensure a pro-active role of the patients' organisations to plug these gaps in terms of our image and 'Made in India' brand."

On the contrary, speaking about the COVID-19 vaccines that are being manufactured in India and are facing hurdles in

getting international approvals, S Srinivasan, Managing Trustee, Low-Cost Standard Therapeutics (LOCOST) and co-Convenor, All India Drug Action Network (AIDAN), states that it is because of the quality and transparency level of clinical trial data -- these need to be in the public domain.

“Lack of transparency creates avoidable buzz and suspicion.

Over and above this, there has been no clear picture about the extent of ADRs caused because of the vaccine or reasons associated with it. At one level, this is also a problem worldwide because of the accelerated paradigm of emergency use authorisation and confounding pictures of the virus' variants,” he says.

In Navangul's opinion, the industry needs to comply with the rules and standards established for vaccine manufacturing and policymakers have to oversee and ensure conformity to those rules and standards.

"Vaccine development is a lengthy, multi-stage process where essential actions need to be taken up synergistically, and hence, industry players and policymakers need to work in tandem and jointly accomplish the goal of accelerating vaccine development. Policymakers should work closely with the industry to evaluate GMP requirements with regard to Quality Risk Assessment," he mentions.

Shankar points out that to improve its global market presence, Indian vaccines need expeditious approvals in larger markets. This goal is possible if, the industry, with assistance from policymakers, collaborates with regulatory agencies of other countries for the exchange of best practices, focussing on the specific issues faced by Indian companies.

He says, "The revision of Schedule M of the D&C Act in line with the global guidelines is a welcome step. However, for high-income countries to readily accept Indian vaccines, manufacturers and policymakers are required to address the shortfalls like insufficient

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cover ) manpower and lack of welltrained and qualified employees -the fundamental cause of GMPs non-compliances. The pharma companies and government need to work together to formulate a systematic programme for regular staff training and monitoring infrastructure. The extensive training has to be imparted not only to the high-level management cadre, but also to the juniorlevel personnel engaged in production, who need the skills for confidence in taking charge of quality controls; constant examination and observation, including surprise audits by the health inspectors, that would help in ensuring quality assurances and effective control systems, and thereby conform to GMP standards at all times; ensuring the highest-quality drug formulation which requires that the pharmaceutical products are GMP-compliant, as per the WHO standards. To ensure the best practice, policymakers, in consultation with all other stakeholders, could set certain pre-qualification assessments before launching the final product. All such measures that sustain GMP compliance have a direct impact on the validation of the safety and efficacy of the vaccines."

The current perception Navangul highlights that the

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Indian pharma companies currently meet more than 50 per cent of the global demand for different vaccines needed for global immunisation problems.

The country had initiated the 'Political Declaration on Equitable Global Access to COVID19 Vaccines' that garnered support from over 180 UN member states.

"India has supplied more COVID-19 vaccines globally than any other country. Companies like SII are manufacturing, developing and commercialising the vaccine in India.

Despite the fact that many countries globally are procuring COVID-19 vaccines manufactured and approved in India, the perception that there are gaps in regulatory robustness still exists. Indigenous vaccine approvals need to be backed with efficacy data to wipe out these perceptions," he asserts.

Shankar, talking about vaccine hesitancy, gives his take on why India's homegrown vaccine had to face scepticism within India and globally.

"Vaccine hesitancy in India was fuelled by concerns over vaccine safety and scepticism about the efficacy of the Covaxin vaccine, which had been hurriedly approved before the completion of the phase-III clinical trials. As public trust in the efficiency of the handling of the pandemic was already at an

all-time low, reports of CDSCO allegedly acting in a manner outside its regulatory purview, and the subsequent opacity in the conduct of the drugmakers, further aggravated public morale, undermining the value of the indigenous vaccines on the international stage," he opines.

However, in a statement released last month, Bharat Biotech had put to rest any concerns on the quality of Covaxin, claiming that every batch of the vaccine is subjected to over 200 quality control tests at the company's facilities, followed by submission samples to Central Drugs Laboratory (CDL), only based on approval/release by CDL, are batches released commercially.

It had also been said that since early June, manufacturing of Covaxin has commenced at its sites at Malur, Karnataka and Ankleshwar, Gujarat, prior to which engineering batches were also executed to study equipment functionality. Products manufactured from these facilities were to be available for supplies during September.

This is based on the company's 120-day timeline for manufacturing, testing, release, regulatory approvals and distribution.

"Vaccine manufacturing, testing and release at Bharat Biotech follow validated, stringent GMP processes which

were established over 20 years, with several billion doses of vaccines supplied within India and globally," informed the company.

Prof Misra provides a counterview and assures that India is perceived as one of the best manufacturers of vaccines globally. He explains that during the COVID-19 vaccines manufactured in India, the country faced several regulatory challenges in the international markets because of the negative propaganda promoted by vested commercial entities to undermine the vaccines as those were competitive and affordable.

"It is most unfortunate that globally India is always projected in a negative manner to mislead the patients globally from accessing our products based on reasons best known to them. There is always a bogey created about our quality and efficacy," he laments.

Mayer says that the Indian vaccine market is still in its infancy, compared to that of other developed countries including the US, Europe, Australia and Canada. The IMARC Group estimates that the Indian vaccine market will reach $1.08 billion by 2021-22 at a CAGR of 17.8 per cent.

"Pharma companies from the US and EU are looking at India as a potential market for generic drugs, especially

vaccines. Efforts are being made by the Indian government to make vaccines affordable and accessible for the masses. However, not all Indian vaccines are perceived the same way in the international markets. On COVID-19 vaccines, there is a pressing need for international coordination.

As UNICEF provides procurement services and WHO provides technical assistance, a global effort is needed to deal with coronavirus that crosses over national interests and mobilises resources in the times of economic recession," he states.

Path to progress The fact remains that a majority of Indian companies involved in the production of vaccines face troubles entering advanced economies. Vaccine producers for medical markets such as the US and EU have found it hard to penetrate these markets due to certain factors including unfavourable regulations, lack of patient compliance and high expenditures.

It's important to work on improving India's infrastructure for equipment and inspections to meet standards and avoid regulatory barriers to consolidate India Vaccine Inc's position in the world markets. akanki.sharma@expressindia.com journoakanki@gmail.com

STRATEGY INSIGHT

Impact of COVID-19 and regulations for OTC segment Many pharma companies are inclined to capture the OTC market in India due to the high consumer ratio, but COVID has shifted the attitude of people for self-medication as well, explains Sanyam Gandhi, Regulatory Affairs Strategy Lead, Takeda Pharma

O

ver the counter (OTC) drugs are medications that are safe and effective for use by the public without seeking treatment by a health professional; for instance, pain relievers, cough suppressants and antihistamines. OTC designation is granted for a pharmaceutical product when enough safety and efficacy data is available, and the product is marketed for a very long time. Any specific help from medical professionals is not required to administer OTC products and it can be bought from pharmacies or online platforms without prescription. Despite being classified as safe, the following might be a few associated risks with the OTC: ◆ Dosage may vary for the pediatric population. ◆ There is a possibility of an allergic reaction. ◆ It may be risky to consume during pregnancy. ◆ The medicine may interact with other medicines, supplements, food, etc.

OTC sales in upcoming years.

Regulation of OTC products In many countries, OTC drugs are selected by a regulatory agency to ensure that they contain ingredients that are safe and effective when used without a physician's care. OTC drugs are usually regulated according to their active pharmaceutical ingredient (API) rather than final products. By regulating APIs instead of specific drug formulations, governments allow manufacturers the freedom to formulate ingredients, or combinations of ingredients, into proprietary mixtures. ◆ Europe: Article 74a of the Directive 2001/83/EC as amended by the Directive 2004/27/EC sets out switching drug products from prescription to OTC. European Medicine Agency

active ingredients and the labelling of over 80 therapeutic classes of drugs, for example, analgesics or antacids, instead of individual drug products. For each category, an OTC drug monograph is developed and published in the Federal Register. OTC drug monographs are a

(EMA) review certain criteria to switch from finished product to the OTC product. ◆ USA: The US Food and Drug Administration's (FDA) review of OTC drugs is primarily handled by CDER's office of nonprescription drugs. The Nonprescription Drug Advisory Committee meets regularly to assist the agency in evaluating issues surrounding these products. This committee has played a major role in the growth of prescription to OTC switches in recent years. There are over 300,000 marketed OTC drug products. FDA reviews the

kind of recipe book covering acceptable ingredients, doses, formulations and labelling. Many of these monographs are found in section 300 of the Code of Federal Regulations. ◆ Australia: The Therapeutic Goods Administration (TGA) Act requires that all medical products to be imported or exported from Australia must be included in the Australian Register of Therapeutic Goods (ARTG). For a medicine to be included in the ARTG, a sponsoring company is required to lodge an application to the TGA. The TGA has developed the Aus-

COVID-19 and OTC OTC is a growing market, and it is expected to grow with a Compound Annual Growth Rate (CAGR) of six per cent during the next few years, globally. The highest growth is expected from emerging markets like Latin America and Southeast Asia.

When compared globally, India is expected to grow by 9.2 per cent and the COVID-19 pandemic has an important role in this forecast. Many pharma companies are inclined to capture the OTC market in India anyway due to the high consumer ratio, but COVID has shifted the attitude of people for self-medication as well. Impact of lockdowns, supply chain disruptions, etc. are also the key factors that will add surge in the

tralian Regulatory Guidelines for OTC Medicines (ARGOM) to assist sponsors of OTC medicines to meet their legislative obligations. OTC medicines can be registered or listed on ARTG, depending on the level of risk associated with making the product available and accessible to consumers. The registered OTC medicines are considered to be of lower risk than prescription medicines, but they still require an appropriate level of scrutiny. ◆ The United Kingdom: The Medicines and Healthcare products Regulatory Agency (MHRA) is an executive agency of the Department of Health and Social Care in the United Kingdom which is responsible for ensuring that medicines and medical devices work, and are acceptably safe. Apart from the prescription category, there are two following categories in the UK. Pharmacy medicines: People can buy products classified as 'pharmacy medicines' (P) but only from a pharmacy and in the presence of a pharmacist. These medicines, also called 'pharmacy-only medicines,' are not usually displayed on open shelves. A rectangular box enclosing the letter P appears on the packaging of pharmacy medicines.

General sale medicines: People can buy general sale medicine packs from retail outlets such as corner shops and supermarkets.

The medicines-also called 'general sales list (GSL) medicines'are also available for self-selection in pharmacies. General sale medicines are taken for common and easily-recognised ailments which usually last around twoto-three days. These medicines cause few troublesome side effects in normal use. ◆ India: Many drugs are sold over the counter without pre-

scription, but the regulatory regime is grey in this regard, primarily because the term OTC has not been expressly defined under the Drugs & Cosmetics Act, 1940 (D&C Act) and the Drugs and Cosmetics Rules, 1945 (D&C Rules). Regulatory ambiguity is set to change, however, as the Central Government is now actively considering regulating the sale and distribution of OTC drugs. The Central government has formed a new three-member sub-committee to expedite efforts to define overthe-counter (OTC) medications that can be sold in the country without prescriptions and put in place a regulatory framework for those. The OTC committee of the Organisation of Pharmaceutical Procedures of India (OPPI) is currently working towards the promotion of responsible selfmedication in order to promote the OTC market. It is also aiming on promoting the importance of responsible self-medication through awareness programmes and community education. The committee not only promotes OTC use, but also emphasises on safety. Besides promoting OTCs, establishing a balance between wider access to drugs and their safety should also be focussed on.

Major countries have defined pathways for the registration of OTC products and India needs to define regulation around it. A regulatory decision as to whether to increase the accessibility of drugs hinges on a determination of whether the benefit to be gained by doing so can be justified in light of any additional risk posed by self-medication.

The ongoing COVID-19 pandemic has restricted the opportunities for formal medical intervention for patients in general and the OTC market is expected to be huge after the pandemic.

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STARTUP I N T E R V I E W

“Counterfeiting is an ongoing menace” Vipin Choudhary, Founder and CEO, PUCHO, informs Akanki Sharma about the impact of counterfeit medicines and how his company is trying to eliminate it, while also adding value to the consumer and brand owner in the process What is the current market potential of anti-counterfeiting solutions for drugs, nationwide as well as across the globe?

The global anti-counterfeit solutions market is expected to grow by $80.88 billion during 2021-2025, progressing at a CAGR of almost 12 per cent during the forecast period. As per a statement released by the United States Trade Representative (USTR), 20 per cent of all pharmaceutical goods sold in the Indian market are counterfeit. India is world's leading producer of fake drugs, according to a research by the Organisation for Economic Co-operation and Development (OECD) and the EU Intellectual Property Office.

Pharmaceutical and medical device industry in our country is $52 billion annually and counterfeiting is growing at an average of 20 per cent year on year.

India, engulfed by the COVID-19 pandemic, pushed people to rush to markets to get medicines, oxygen cylinders, masks, PPE kits and other essential life-saving equipment. The crisis and an acute shortage of drugs and medical devices to treat symptoms of COVID-19 unfortunately increased the circulation of counterfeit medicines and medical devices in recent times.

While COVID-19 is a current pandemic, counterfeiting is an ongoing menace.

What prompted you to come up with PUCHO, and for how long has it been active now? How many users do

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The impact of counterfeit on the consumer, brand owner, the environment, economy, employment, health and the country is unimaginable. Thirty to 40 per cent of products sold in India annually are counterfeit you have till date?

I started working on a counterfeit solution in 2015 to address counterfeit in agrochemicals, which negatively impacts 65 per cent population's (farmer) income by losing almost 70 per cent of crop yield,

contaminates the produce which eventually causes longterm health problem for people consuming the produce, impacts country's food production capability and much more.

The impact of counterfeit on the consumer, brand

owner, the environment, economy, employment, health and the country is unimaginable. Thirty to 40 per cent of products sold in India annually are counterfeit. However, in the course of journey, I realised counterfeit medicine kills more people than malaria every year. Counterfeit COVID vaccines, medicines and medical equipment are already flooding the market.

So, our industry focus changed to giving priority to pharma sector. Though, our solution can be used for all industries. We launched our solution on 1st August, 2021 and are already in discussion with many large pharma companies and even pharma associations.

Our advanced AI system reacts in real time to counterfeiter's attempts to replicate our noise print feature, making sure not just to protect the integrity of the product, but also to discourage attempts to create fakes while collecting valuable data on the counterfeiters.

Our mission is to eliminate counterfeit by adding value to the consumer and brand owner in the process.

Why does counterfeit continue to grow despite certain anti-counterfeit solutions being available in the market for decades?

Bar codes, holograms, 3d holograms, etc. were invented for data storage for supply chain, and do not work as anti-counterfeit solution as those can be easily copied.

Even bar codes with unique numbers don't work as anticounterfeit solution. There is a 50 per cent chance of counterfeit being sold as

original. The Radio Frequency Identification (RFID) also has a limited industry application, and is too expensive. It is meant for inventory management and track and trace, and is not effective as anti-counterfeit solution.

Apart from it, even invisible ink cannot be used by consumers to authenticate with naked eye, while scratch cards are something that a consumer can identify only after purchase.

How does PUCHO function?

Tell us about your AIpowered noise print anticopy labels to eliminate counterfeit. How can this be of help to pharmacists?

PUCHO offers the only anticounterfeit solution that has been ISO 12931-certified, which comprises AI-powered noise print anti-copy labels to eliminate counterfeit, a multilingual app powered by Cypheme, a globally renowned AI and brand protection solution to protect drugs and medical device brands against the growing menace of counterfeits.

PUCHO's AI technology can also help identify fake COVID19 vaccines. The result comes in multiple (15 vernacular) languages with an audio button for the consumer to hear the result.

PUCHO functionality is simple: scan - authenticate buy. No brand owner wants to sell and no consumer wants to buy counterfeit medicine.

Counterfeit happens in the journey of medicines from brand owner to retail shops, and ultimately counterfeit medicine reaches the consumer.

We have put the power in

the hands of brand owner as well as the consumer - the brand owner affixes our noise print label and the consumer scans the label before purchasing the medicine.

Each noise print label has a unique and random chemically-generated signature that can be scanned, but cannot be copied. The noise print feature is managed by advanced neural network algorithms that detect change in any of the AI security labels administered to products in the open market. We will know when and how a counterfeiting attempt is made on the product and can take the necessary steps to prevent the counterfeiters from advancing.

PUCHO provides the brand owners dashboard with data of authentic and counterfeit product scans with geo-location hotspots for targetted action against counterfeiters The pharmacists and hospitals can authenticate the medicine before selling/administering to the patient. Consumers can authenticate before purchase, even the investigators, mystery shoppers of brand owners can authenticate the product via a simple scan through our app - PUCHO. PUCHO provides the brand owners dashboard with data of authentic and

counterfeit product scans with geo-location hotspots for targetted action against counterfeiters.

What are the existing challenges to the growth of anti-counterfeit solutions for medicines in India and across the world? What immediate steps are you taking to overcome these?

There are two challenges in combatting counterfeit

medicines: lack of solution to authenticate "before purchase" and single platform to authenticate products from different companies/brand owners.

Our solution solves both these problems. We strive to make our technology simple and easy to use for a consumer. We focus on consumer-authentication before purchase. It is critical to empower consumers so

that they can buy smart and keep themselves safe from counterfeit medicines.

Tell us about your business expansion plans.

We are in discussion with various pharma and medical devices companies and also pharma industry associations, giving product demos. The response is encouraging and engaging, as, apart from saving lives, it will also help pharma companies regain the revenue lost to the counterfeiters. By the year end, we intend to have this solution implemented on all critical drugs and COVID medicines. akanki.sharma@expressindia.com journoakanki@gmail.com

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September 2021

PHARMA PACKAGING I N T E R V I E W

Pharma sector needs to be sustainable with green and eco-friendly packaging The role of the manufacturers, policymakers and reinsurers is vital in adopting glass as a better lifestyle option and help India achieve its global vision to replace plastic with green and eco-friendly packaging, informs Rrajesh Khosla, President and CEO, AGI glaspac, to Viveka Roychowdhury in an exclusive interaction What are the most important factors to consider when designing packaging for the pharma industry?

Pharmaceutical packaging is a heavily regulated field. Any materials used in the packaging must protect the contents against contamination and degradation. With tamperevident and child-resistant closures, glass is a feasible option for pharmaceutical packaging. Further, it is the only packaging material with GRAS status from the US FDA. Pharma containers are generally in amber-coloured glass to prevent light transmission that will affect the formulation. Therefore, it is important that cleanroom environment is there for pharma glass manufacturing to prevent contamination in glass bottles. Pharma bottles have non-returnable properties; hence, those are produced at the lowest possible weights and with uniform thickness. With the assistance of advanced blowblow and NNPB technologies, bottles are produced with airtight packaging and delivered to the purchasers.

AGI today melts over 1600 tonnes of glass per day and has been heavily investing in R&D, machine-building and business excellence capabilities to maximise productivity and upgrade the plant. It is also investing in technology upgrades, inspection, packaging systems, warehousing and logistics

Did pharma companies start to properly implement ecofriendly practices into their core business model?

Pharma companies are one of the major contributors to climate change and plastic waste. Although, for many years, the impact of

healthcare on the environment was overlooked in the pharma sector, awareness of the sector's carbon footprint has now grown. Being eco-friendly has become a huge issue. With the consumers becoming more cautious, pharma companies

34 EXPRESS PHARMA September 2021

are cognizant of the environmental factors. We are exploring how packaging can help to solve this issue through innovative design for reducing wastage.

Is the healthcare industry becoming more sustainable?

As a result of environmental concerns, there has been a growing interest from the healthcare sector to become more sustainable. Companies must start linking sustainability to their economic value in the long term. It will enable pharma companies to introduce bold and eco-friendly practices into their core business model.

Pharma companies can partner with the packaging industry to design or redesign their product packaging to support compliance while simultaneously switching to more eco-friendly alternatives to plastics.

How are companies like AGI glaspac propagating India's dream and global vision to replace plastic with green and eco-friendly packaging?

AGI has positioned itself as one of the leading container glass manufacturers in the country with two manufacturing facilities, one in Hyderabad and one at Bhongir (Telangana). AGI today melts over 1600 tonnes of glass per day and has been heavily investing in R&D, machine-building and business excellence capabilities to maximise productivity and upgrade the plant. It is also investing in technology upgrades, inspection, packaging systems, warehousing and logistics. Besides, it is looking at increasing its volumes by at least 50 per cent to meet the rising market demand in the

next five years. We are at the forefront of offering innovative and light-weight containers to the pharma industry.

What does AGI glaspac do to prioritise sustainability?

AGI glaspac uses the latest technologies to integrate its R&D, production, etc. We have adopted Windchill, which is a product life-cycle management tool that integrates all the stakeholders of the operations right from new product development to bottle packaging. The SAP system is in use to track everyday operations' metrics and quality parameters. The business excellence team is equipped with all the tools required for effective statistical analysis and the development of new methods for sustaining the improvements.

AGI has recently provided the following packaging solutions to its clients: ◆ Offering a new tempering method for strengthening glass containers ◆ Creating a lightweight container in different geometric shapes ◆ Using newer technologies like single-stage forming to produce thinner but stronger glass containers ◆ Developing a coating on the surface of the glass to avoid strength loss ◆ Creating heat-resistant pyrex glass ◆ Creating internal embossing glass bottles

Has the COVID-19 pandemic and production of the vaccine affected the way packaging is designed for the healthcare industry?

During the COVID-19 pandemic, the pharma industry went through various operational changes. The massive scale of the COVID-19 vaccination has placed extreme pressure on packaging manufacturers and the supply chain. However, everyone in the industry has worked vigorously to deliver these volumes without compromising on safety or quality.

While the industry plans to boost its capacities in API and bulk drugs, it encountered environmental issues such as liquid, solid and air pollutants generated during the process.

The immediate need is to put in place a mechanism to process this waste into less harmful substances. The carbon footprint can be better managed by the use of new, improved and technologydriven packaging techniques.

Pharma companies need to consume resources like water efficiently and evaluate the environmental impact of every stage of the product life cycle until its final disposal.

How is recyclability in the

During the COVID-19 pandemic, the pharma industry went through various operational changes. The massive scale of the COVID-19 vaccination has placed extreme pressure on packaging manufacturers and the supply chain pharma sector handled?

It is more important than ever for pharmaceutical companies to plan for recyclable packaging. At this moment, it is important to capitalise on effective technical solutions.

Glass packaging also has other major competitors from other sorts of packaging in India.

The pharma industry is additionally on the lookout for various alternative materials for commercial reasons."

Various reasons for pharma companies to switch are loadbearing ability, breakages and unit cost. Glass manufacturers are developing light-weight and durable bottles for pharma companies to compete with other alternatives.

In future, we should focus on plastic neutrality, water sustainability and green infrastructure.

Does implementing green and eco-friendly packaging

entail adding different packaging lines? Is there an initial upfront cost that makes it more expensive during the initial months?

Almost every step of the manufacturing and production process for ecofriendly products is more expensive than traditional products, from sourcing raw materials to shipping the final product.

A few reasons for this are(a) It is more expensive to grow and manufacture sustainable materials. ◆ Certifications from reputable third parties, such as organic or fair trade, are not cheap. ◆ Growing organic materials is more expensive, in part because pest control alternatives are used instead of chemicals. (b) Many eco-friendly companies will accept and honour the cost of paying workers a fair wage.

◆ Producing an eco-friendly product requires more time, and productivity is affected. ◆ Eco-friendly products are currently more expensive than traditional products due to lower demand and higher production costs.

Has there been a hesitation on the part of pharma/biopharmaceutical companies to switch to ecofriendly packaging? If so, how can those be convinced?

As any business continues to form progress in sustainable efforts, the packaging is one among the most important ways to form an impression.

Organisations have realised that the centrality of sustainability is resilience.

The pandemic has reinforced the idea that sustainability goals can be achieved. As the pharma sector battles the COVID-19 impact and goes through a reset to defend the world

against such crises in future, it needs to be sustainable.

Can policymakers, reinsurers, etc., nudge the industry into adopting ecofriendly packaging practices? Have there been such instances globally?

The recycling infrastructure is still underdeveloped in India. Hence, the role of the manufacturers, policymakers and reinsurers is vital in adopting glass as a better lifestyle option and help India achieve its global vision to replace plastic with green and eco-friendly packaging.

Several pharma companies around the world are pledging and taking essential steps towards key sustainability goals. Various companies in India are also making it a priority. For example, LANXESS, a speciality chemicals company, has linked the compensation package for its board of management to the achievement of the company's sustainability goals. Going forward, the company's performance in the areas of climate protection and occupational health and safety will be of utmost importance. viveka.r@expressindia.com viveka.roy3@gmail.com

CONTRIBUTOR’S CHECKLIST ❒ Express Pharma accepts editorial material for

❒ We welcome information on new products and

regular columns and from pre-approved contributors / columnists. ❒ Express Pharma has a strict non-tolerance policy of plagiarism and will blacklist all authors found to have used/refered to previously published material in any form, without giving due credit in the industryaccepted format. All authors have to declare that the article/column is an original piece of work and if not, they will bear the onus of taking permission for re-publishing in Express Pharma. ❒ Express Pharma's prime audience is senior management and pharma professionals in the industry. Editorial material addressing this audience would be given preference. ❒ The articles should cover technology and policy trends and business related discussions. ❒ Articles for columns should talk about concepts or trends without being too company or product specific. ❒ Article length for regular columns: Between 1200 1500 words. These should be accompanied by diagrams, illustrations, tables and photographs, wherever relevant.

services introduced by your organisation for our various sections: Pharma Ally (News, Products, Value Add), Pharma Packaging and Pharma Technology Review sections. Related photographs and brochures must accompany the information. ❒ Besides the regular columns, each issue will have a special focus on a specific topic of relevance to the Indian market. ❒ In e-mail communications, avoid large document attachments (above 1MB) as far as possible. ❒ Articles may be edited for brevity, style, and relevance. ❒ Do specify name, designation, company name, department and e-mail address for feedback, in the article. ❒ We encourage authors to send their photograph.

Preferably in colour, postcard size and with a good contrast.

Email your contribution to: The Editor, Express Pharma, Business Publications Division,

The Indian Express (P) Ltd, Mafatlal Centre, 7th floor, Ramnath Goenka Marg, Nariman Point, Mumbai 400021 viveka.r@expressindia.com viveka.roy3@gmail.com

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Harmful Side Effects of Preservatives

India’s first ever Preservative Free Ophthalmic Manufacturing Facility Widely accepted

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Patented Pure Flow Technology For contract manufacturing contact: Kilitch Healthcare India Ltd. 902/B Godrej Colesium, Behind Everad Nagar, Near Priyadarshani Cirlce, Sion (East), Mumbai – 400022.

Tel. : 022 6137 2222 Mr. Divya Mehta : +91 9819724957 www.kilitchhealthcare.com info@kilitchhealthcare.com

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To Advertise in

Business Avenues

Email: rajesh.bhatkal@expressindia.com rbhatkal@gmail.com

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EXPRESS PHARMA OsmoTECH® XT Single - Sample Micro-Osmometer Now available!

Best-in-class osmolality performance, designed with you in mind.

HIGHLIGHTED FEATURES:

®

®

®

Offers the widest range of osmolality testing (0 – 4000 mOsm/kg H2O) Supports 21 CFR part 11, GMP and EU Annex 11 compliance Meets Pharmacopeia osmolality testing guidelines 3 Level user access and password protection Storage: unlimited data storage for access Audit trail: Preserve unlimited results and events Database backup, protects your data with automatic or manual backup

No. 127, Bussa Udyog Bhavan, Tokershi Jivraj Road, Sewri West, Mumbai-400015, Maharashtra, Landline : +91 022 - 24166630 Mobile : +91 9833286615

Lab scale & Pilot scale Filtration Test Facilities The selection & sizing of an optimal filtration system can be done by conducting trials on representative samples. Simulation of operating parameters is done while conducting trials which help in generation of accurate data. Trials give us an insight into the fluid characteristics & the problems faced during filtration. This helps in selection of the correct M.O.C, type & grade of filter best suited for the application.

We understand & recognize the importance of testing & have set up a test facility in our premises.

This Test facility is a first of its kind offered in the industry.

Lab scale trials can be conducted with small volume samples. The information gathered from lab scale trials is used as a foundation for subsequent pilot scale trials. The pilot scale test facility in our premises allows customers to conduct trials with 80-100 liters volume. Different types of filters can be tested, while monitoring the differential pressures, flow-rate, clarity etc. Scale-up for plant scale design is done after analyzing the data generated during pilot scale trials.

Our state of the art laboratory is equipped with a high precision laser particle analyzer which works on the principle of laser diffraction. It detects Lab scale testing particle sizes as fine as 0.04 micron & provides a graphical/tabulated data of the particle size as well as its percentage quantity.

Automatic Integrity Test Machine

Laser Particle Size Analyzer

This data helps greatly in determining the various grades of filters required to trap the particles, which is essential for recovery of expensive products or noble metal catalysts.

This emphasis on testing during design stage, coupled with our vast experience since 1978, helps us to offer truly customized solutions to our customers’filtration problems.

Kumar Process Consultants & Chemicals Pvt. Ltd. 4 & 5, Bhagtani Enclave, Sonapur Lane, Off. LBS Marg, Bhandup (West), Mumbai - 400 078. INDIA. Tell. : 911 - 222 - 35552 35562 Mobile: 90047 06047, 98923 12343 email: info@kumarfilter.com www.kumarfilter.com

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Pilot Scale test Facility

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PHARMA PULSE

Complete pharma solution - testo Saveris Pharma testo Saveris Pharma aids in uninterrupted monitoring of various applications in the pharma industry

A

sector like pharmaceuticals, which is governed by strict norms and regulations must operate with utmost efficiency. Testo provides the best-in-class solution for comprehensive automated data monitoring management for equipment and environmental parameters in pharma industry called as the testo Saveris Pharma, an automated system that is integrated in the facility and constitutes of wireless or Ethernet probes installed at different locations that are connected to one base station to document and monitor all measurement data of its own. The monitoring process is uninterrupted, and the system provides a number of alarm options in case the measurement values violate the defined limit values. Some advantages of testo Saveris

Pharma for environment and equipment monitoring system include the following: ◆ Holistic system comprising sensors, software, and services ◆ GxP & 21 CFR Part 11 compliant system ◆ It provides seamless recording and automated documentation, and reduces human ef-

56 EXPRESS PHARMA September 2021

Testo Saveris Pharma aids in uninterrupted monitoring of various applications in the pharma industry.

Application areas ◆ Manufacturing/production area ◆ Research and QC labs ◆ Cleanrooms and data centres ◆ Warehouses and packaging ◆ Deep freezers, refrigerators and cold rooms ◆ Incubators, stability test and walk-in chambers ◆ Blood and tissue banks ◆ Autoclaves and nitrogen tanks ◆ Sterilisers and many more Our specially GxP-trained service team supports you throughout the process in a systematic way - from planning, documentation, system qualification and software val-

forts ◆ Creates uninterrupted documentation through secure triple layer storage of the measurement data ◆ The data is stored in the probes, so even if software connectivity is lost, the data is safe and can be downloaded once the software is logged in

◆ Real-time alarm facility to highlight unexpected results Testo Saveris Pharma system consists of testo Saveris base V 3.0 which is the core component of the system. It manages and evaluates data from all over the facility from 3,000 channels. The four testo 150 data logger modules can

be flexibly combined with the three communication modules (WLAN, LAN and testo UltraRange) making it a convenient and user-friendly system along with the web-based, intuitive cockpit to detect alarms, initiate corrective measures and to acknowledge those, whenever necessary.

idation to service and support.

Testo also has a NABL-accredited service and calibration lab that takes care of the aftersales support locally from Pune.

For more details, login to www.testo.com or write on info@testo.in

L-HPC: Multi-functional excipient Nilesh B Mahajan,Application Development Manager,Shin-Etsu Chemicals,India informs that his company offers application-specifc selection of suitable L-HPC grades

T

he oral route is the most common route of drug administration for various pharmaceutical dosage forms because of patient compliance, ease of administration and safety. The most common forms available are tablets, powders and capsules. As new pharmaceutical formulations continually emerge over the

L-HPC - Dual functional excipient as disintegrant and binder

wet granulation techniques like high shear mixer granulation, fluidised bed granulation and twin-screw granulation. In wet granulation, L-HPC gives a buffer effect stabilising the wet massing process for a wide range of water content. Further, it offers good tablet hardness with quick disintegration and stable formulation.

L-HPC is not the same as Hydroxypropylcellulose (HPC).

Although sharing the same CAS number, L-HPC has different characteristics as compared to HPC, that is a binding agent widely used for solid dosage forms.

lower friability.

Drug layering: Addition of L-HPC in drug layering can give coated pellets with less friability without delaying disintegration. L-HPC being non-ionic in nature, there is minimal interaction with API. Based on the application, Shin-Etsu can offer a variety of L-HPC grades.

SOLID DOSAGE FORMS: TABLETS AND PELLETS L-HPC Grade

All Anticapping

Wet Granulation Dissolution improvement

Shorter DT*

Direct Compression Binding

Shorter DT*

Binding

Dry Granulation Binding

Others Pellet extrusion

LH-11

VS

LH-21

S

S

S

S

S

LH-22

S

S

S

S

S

LH-B1

Drug layering

ODT

VS

VS

VS

S

LH-31

S

S

S

VS

S

S

LH-32

S

S

S

VS

S

S

VS

VS

VS

VS

S

S

VS

VS

S

VS

VS

VS

VS

NBD-020

S

NBD-021

S

NBD-022

S

*DT: Disintegration time, S: Suitable, VS: Very suitable years, there is a need for the introduction of multi-functional pharmaceutical excipients such as Low-substituted Hydroxypropyl Cellulose (L-HPC) which has applications in various commonlyused pharmaceutical manufacturing process techniques.

L-HPC was first approved in 1977 as a disintegrant for pharmaceutical solid dosage forms in Japan. A recent survey shows that it is ranked as the first choice for tablet disintegrant by Japanese pharmaceutical companies. Not only a disintegrant, L-HPC also functions as binder due to its good compressibility. In addition to conventional L-HPC grades, NBD grades, which have improved flowability and compressibility, were newly introduced in 2011.

L-HPC and HPC have separate monographs in pharmacopeia. While the regular HPC has a large amount of hydroxypropoxyl groups in the cellulose backbone, LHPC has only a small level.

Due to this chemical difference, HPC is soluble in water, but L-HPC is insoluble. HPC is typically used for granulation binding as an aqueous solution, but L-HPC cannot be used in this way. L-HPC is an effective disintegrant due to its swelling action in water, but this is not the case with HPC. This is because L-HPC also has good compressibility, dry blending of this material produces hard tablets like those made from microcrystalline cellulose. In this application, L-HPC functions as a "dry binder."

Key benefits of L-HPC

L-HPC applications Direct compression: L-HPC NBD grades are commonly used in direct compression as these have narrower particle distribution and better flowability that enables to make less variation on tablet weight and drug content.

Wet granulation: L-HPC grades are suitable for various

Pellet extrusion: Micronised grade of L-HPC is more suitable for this application.

Addition of L-HPC enables wet mass to accept a wider range of water content resulting in greater extrusion speed and yield, and thus an overall increase in productivity. The final pellets show quick disintegration and

◆ High stability due to its non-ionic nature and low water activity ◆ No peroxide offers superior stability ◆ Disintegration into smaller particles leading to better dissolution ◆ Anti-capping effect for tableting process ◆ Suitable for pellet extrusion as well as tableting ◆ A variety of grades are available depending on application ◆ Pharmacopeial compliance as per NF, EP, JP and 21 CFR 172.870 (Code of federal register/food additives) For more info, please contact : pharmaindia@setylosein.com or visit https://www.metolose.jp/en

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PHARMA PULSE

Yokogawa begins work on inter-industry collaboration study project for realisation of carbon-neutral industrial complex Decarbonisation through the effective use of CO2 emissions

Y

okogawa Electric Corporation has begun working on an inter-industry collaborative study project for the achievement of carbon neutrality at an industrial complex in the Goi district of Ichihara city in Chiba Prefecture. The study will examine the feasibility for collaboration by companies in different industries in a carbon-recycling business, and will involve surveys on the current status of the energy balances of their industrial plants and the capture and reuse of the carbon dioxide (CO2) emitted by those. The goal for this project is to lay the groundwork for a business that will aim to achieve net-zero CO2 emissions for the entire industrial complex by 2050.

This study has been commissioned by the New Energy and Industrial Technology Development Organization (NEDO).

In line with the international community's efforts to address climate change, the Paris Agreement was adopted at the 21st Conference of the Parties to the United Nations Framework Convention of Climate Change (COP 21), with the signatories agreeing to reduce greenhouse gas emissions to virtually zero by the second half of this century.

According to an International Energy Agency (IEA) report, carbon capture, utilisation and storage (CCUS) technology that captures CO2 emissions from power and other industrial plants as well as CO2 in the atmosphere will account for approximately 15 per cent of the cumulative CO2 reduction needed to achieve CO2 net-zero emissions by the year 2070. Japan has declared that it will achieve carbon neutrality by 2050. As per an an-

58 EXPRESS PHARMA September 2021

community, and contribute to the achievement of a carbonneutral society that is one of the company's "three goals" for sustainability.

Project details

Inter-industry collaboration in a carbon recycling business

The goal for this project is to lay the groundwork for a business that will aim to achieve net-zero CO2 emissions for the entire industrial complex by 2050 nouncement by the Ministry of Economy, Trade and Industry in December 2020, carbon recycling plays a key role in Japan's Green Growth Strategy, and innovation in this field through public-private partnerships are encouraged.

After this study was commissioned by NEDO in February, Yokogawa contacted and requested the cooperation of companies in the Goi district and its neighbouring districts that operate plants with high CO2 emissions, and also conducted a survey of CCUS technologies and other subjects.

Yokogawa will begin collaborating with these companies to ex-

amine the feasibility of a carbon recycling business, focussing on the three aspects of the effective use of materials and energy, CO2 capture and utilisation, and hydrogen management.

For this study, the company will leverage expertise held throughout the Yokogawa Group, including that of the subsidiaries Yokogawa Solution Service Corporation and KBC Advanced Technologies.

Specifically, Yokogawa will make use of the knowledge of manufacturing processes that have been cultivated through work for many different types of plants both in Japan and

overseas, expertise in the improvement of processes and energy efficiency for single sites as well as the integration of multiple industrial sectors' sites, virtual power plant technologies that enable the control of supply and demand at the regional level, regional energy management systems that optimisse control based on supply and demand, and simulation technology that supports the execution of optimal production planning.

By cooperating with partners in the survey across multiple industries, Yokogawa is aiming to achieve net-zero CO2 emissions for the entire

◆ Project name: Carbon recycling and next-generation thermal power-generation technology development /next-generation thermal power-generation technologypromotion business/ feasibility study of carbon recycling business utilising inter-industry collaboration in industrial complexes, etc./inter-industry collaboration study project in the Goi district of Chiba Prefecture ◆ Project period: FY2020 to FY2022 Yokogawa provides advanced solutions in the areas of measurement, control and information to customers across a broad range of industries, including energy, chemicals, materials, pharmaceuticals and food. It addresses customer issues regarding the optimisation of production, assets and the supply chain with the effective application of digital technologies, enabling the transition to autonomous operations.

Founded in Tokyo in 1915, Yokogawa continues to work towards a sustainable society through its 17,500 employees in a global network of 119 companies spanning 61 countries.

For more information, visit www.yokogawa.com The names of corporations, organisations, products, services and logos herein are either registered trademarks or trademarks of Yokogawa Electric Corporation or their respective holders.

PHARMA PULSE

Keeping up the momentum of innovation To leverage growth opportunities,medical device manufacturers must focus on enhancing productivity and throughput,reducing cost and wastage,and improving quality and reliability

W

orldwide, the healthcare and medical device manufacturing industry has been growing significantly in the last couple of decades. Talking about India, it comes among the top 20 markets for medical devices worldwide.

As per a report, India's medical devices market was at $11 billion in 2020 and is expected to grow by $65 billion by 2024. However, there is a massive gap in the demand and supply of these devices in the country.

Many domestic and international medical device manufacturers are currently chasing the significant opportunity for manufacturing devices in India. To leverage growth opportunities, manufacturers must focus on enhancing productivity and throughput, reducing cost and wastage, and improving quality and reliability. With smaller batches, customised medicines and a never-ending process of optimising TCO and OEE, the need for adaptive solutions in the production of medical devices has never been more urgent. To achieve this, we have many production and assembly technologies available in India.

Forward-thinking products and solutions are essential to the worldwide success of medical device manufacturers - while quality and robustness directly impact day-to-day operation.

However, while positioning themselves for long-term success on the global market, medical device manufacturers face particular challenges for further development. To be successful, these manufacturers need to address the challenge of rapidlychanging demand.

Medical device manufacturing challenges Medical device manufacturers produce high-value and sophisticated devices used in shortterm and long-term healthcare requirements. Along with the entire manufacturing process, these products are highly regu-

cient and economical mass customisation and creates possibilities for efficient in-line quality checks that assure 100 per cent quality while maintaining production speed and reducing loss during production.

The backbone of an adaptive machine is an intelligent track system, which consists of individually-controlled shuttles running on an array of electromechanical tracks. Although a track system may appear deceptively similar to a conventional assembly line at first glance, it provides the unprecedented capability to run multiple product types simultaneously, among the features that make this possible to divert shuttles around one workstation to another.

Each of the independentlycontrolled shuttles follow their unique path through the line, skipping some stations and visiting others as needed. Load-balanced parallel stations maximise output per square metre of floor space. Divergent flows merge on the fly to form custom kits and packs at full production speed all perfectly orchestrated by a central control system.

Choosing the right track system

lated and demand rigorous quality control and proper documentation of all operations. In addition to this, manufacturers face some practical challenges like: ◆ Make-to-order vs. make-tostock ◆ Custom devices and kits ◆ GAMP compliance and serialisation ◆ Streamlined assembly ◆ Instant changeover without human intervention ◆ Reducing operational costs and dependence on inconsistent manual labour By implementing effective adaptive manufacturing processes, leaders in medical device assembly can address these

challenges.

Adaptive machine technology: New flexibility in medical device assembly Leaders in medical device assembly create solutions with the extraordinary ability to produce multiple product types - enabling small-batch flexibility without compromising productivity. This new generation of adaptive machines is uniquely efficient at automating dynamic changes-the secret: a synergy of crucial technology breakthroughs integrated into a single system.

Adaptive manufacturing

makes a significant contribution when individual parts are assembled to make the products used for medical treatments; for example, a catheter, syringe, or infusion set. All these tubes, valves and needles were produced separately and needed to be put together. This process is called medical device assembly and can benefit enormously from adaptive machine technology.

An adaptive machine can divert individual products from the production flow - for any reason, at any time - without interfering with the overall production.

This sets the stage for effi-

Depending on the type of medical device that is being produced, there is a wide range of solutions to address challenges that would be difficult, if not impossible, to solve using a conventional approach. B&R's innovative track systems make it possible to manufacture small batches and individualised products, economically. ACOPOStrak, SuperTrak and ACOPOS 6D transport work through a machine individually without being bound to rigid timing, resulting in unprecedented productivity. These mechatronic systems are explicitly developed for 24/7 industrial operation. They are designed for high availability under demanding conditions. With Continued on Page 60

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Sigachi and Aga Khan Rural Support Programme India launch Integrated Development Programme The programme primarily aims at improving nutrition,drinking water and hygiene conditions, sanitation and access to renewable energy to more than 1,000 tribal households spread across five villages in the Bharuch and Narmada districts of Gujarat

S

igachi Industries (Sigachi) and Aga Khan Rural Support Programme India (AKRSPI) have come together to launch multi-year Integrated Development Programme in Bharuch and Narmada districts, Gujarat. The programme primarily aims at improving nutrition, drinking water and hygiene conditions, sanitation and access to renewable energy to more than 1,000 tribal households spread across five villages of the two districts.

Signing the Memorandum of Understanding (MoU) on behalf of Sigachi at the launch event, Amit Raj Sinha, MD and CEO, Sigachi, was quoted as saying, "Launching Integrated Development Programme with reputed partner in AKRSPI brings me lot of joy and hope. In such unprecedented times we are living in, I am grateful that Sigachi is being able to contribute to nation building and well-being of communities around our units

through channels like this. On behalf of my entire team, I would like to congratulate AKRSPI for excellent planning phase. I am confident that we shall achieve programme objectives and set these five villages as role model

villages with help of community."

The MoU was signed by Apoorva Oza, CEO, AKRSPI, on behalf of AKRSPI. A well-known face in development sector, Oza was quoted as saying, "The tribal regions of Gujarat are among

the poorest in the state despite being blessed with natural resources and a united community.

We are thankful to Sigachi Industries for their support which will enable us to work for these communities and improve the

quality of their lives."

The company is proposing a public issue of its equity shares and has filed a draft offer document and the same is available on the website of SEBI, stock exchanges and the BRLM.

in perfect synchronisation with zero waiting time generates higher productivity and takes OEE to new heights. A machinecentric robotics solution plays an essential role in producing more medical devices per m² floorspace.

ket. Digital twins also allow ready reconfiguration of the installed track system's modular components to adapt to new applications quickly. And, digital twins provide built-in documentation for system planning and validation. These end-user simulation and configuration tools make implementing the latest technologies much easier without steep learning curves.

automated track technology.

Manufacturers who have already installed these types of track technology are ripping the benefit of improved productivity and reduced cycle time.

The coming years have massive potential for quality medical device manufacturing. The Indian manufacturing industry will be a good ground for all medical device manufacturing companies.

Along with the available technological advancements, the government schemes to establish deeper acquaintances with the current market will attract numerous medical giants to set up their activities in India.

Keeping up the...

Continued from Page 59

Full integration of robots

the next-generation industrial transport technology such as ACOPOStrak, SuperTrak and ACOPOS 6D, B&R is redefining the future of transport technology by enabling machine builders to achieve higher OEE, smaller machine footprint, batch size one production, mass customisation, shorter time to market, and can further accelerate their return on investment.

These technologies enable adaptive manufacturing and are a generation leap ahead of the market.

Robots create big advantages for medical device assembly in terms of both, production efficiency and total cost of ownership. With machine-centric robotics, B&R has taken another big step towards higher productivity and efficiency. The solution saves floorspace and streamlines spare parts inventory by eliminating the need for a dedicated robot controller. There's no longer a need for separate hardware and separate communication. The machine doesn't need to wait for the robot, nor does the robot need to wait for the machine. Simultaneous movements

60 EXPRESS PHARMA September 2021

The role of the digital twin Different shuttle configurations and track layouts of transport technology can be simulated using a digital twin. It helps to optimise line performance before any commitment to capital expenditure is made. Virtual commissioning reduces the total cost of engineering and time to mar-

Your competitive advantage With this backdrop, medical device manufacturers can explore innovative ways to improve productivity and flexibility using

PHARMA PULSE

Pycnogenol®: the Vascular Multitasker In numerous studies,Pycnogenol® has been shown to normalise blood pressure and platelet function and to improve blood lipid as well as blood sugar values. Dr Franziska Weichmann,Manager, Scientific Communications and Product Development,Horphag Research,explains more

K

eeping a healthy cardiovascular system is key for maintaining good vitality, physical strength, mental health and for general wellbeing. According to the Global Atlas of Cardiovascular Disease 2000-2016, cardiovascular diseases (CVDs) accounted for 20% of the total burden in women and 24% in men(1). Cardiovascular disease is the leading cause of death worldwide, accounting for 31% of total causes of death(2). Most cardiovascular diseases are preventable, leaving only few possible risk factors beyond our control, such as the normal ageing process and gender. The leading cardiovascular risk factors are high blood pressure (with 13% of global death attribution), cigarette smoking (9%), high blood sugar (6%), sedentary lifestyle (6%), obesity (5%), high cholesterol (5%) and alcohol or drug use (4%)(2).

Pycnogenol® French maritime pine bark extract, as part of a healthier lifestyle, may significantly contribute to the improvement of some of these vascular risk factors. In numerous studies, Pycnogenol® has been shown to normalise blood pressure and platelet function and to improve blood lipid as well as blood sugar values. An ever-increasing number of clinical studies demonstrate the efficacy of Pycnogenol® for keeping cardiovascular health problems at bay. The effect of Pycnogenol® was investigated in healthy people, individuals with borderline high-risk factors but also as an adjunct in people taking prescription medicine for cardiovascular health issues.

Improved endothelial function One of the key properties of Pycnogenol® is its effect on endothelial health(3-9). The most important vascular mediator

and major cardiovascular signaling molecule in the endothelium is the nitric oxide (NO).

NO contributes to optimal blood flow by relaxing blood vessel walls, when necessary, for a more fluid blood flow. In addition, NO helps prevent blood platelet aggregation, thus reducing the risk of thrombosis

flow-associated shear stress)(5).

This 8-week randomised, double-blind, placebo-controlled cross-over study showed that flow-mediated dilation was improved by 32% in the Pycnogenol® group, whereas it slightly decreased in the placebo group.

In another double-blind

lowered by 17.8% compared with scarcely any change in placebo patients.

In borderline hypertensive, hyperlipidemic and hyperglycemic patients, flow-mediated dilatation significantly improved after 8 and 12 weeks of Pycnogenol® supplementation (9) . These studies confirm the

line hypertension patients(14).

Pycnogenol® supplementation for 8 weeks significantly lowered blood systolic blood pressure compared to placebo. Diastolic pressure was found to be lowered as well.

In the study mentioned above with hypertensive patients receiving treatment with

. Aging or conditions such as hypertension, atherosclerosis or diabetes may negatively affect the endothelium's ability to produce NO, and the responsiveness of blood vessels to NO may decline too(11, 12). This results in chronic blood vessel constriction, which, in turn, impairs blood flow, elevates blood pressure and increases the risk for thrombosis.

Pycnogenol® was shown to enhance endothelial NO generation from the precursor molecule L-arginine by stimulation endothelial NO synthase (eNOS), leading to an increase in blood vessel lumen and adequate tissue perfusion(3, 4).

In patients with coronary artery disease, the effect of Pycnogenol® on endothelial function was assessed by measuring the flow-mediated dilatation of the brachial artery (the widening of the artery in response to elevations in blood

placebo-controlled randomised 12-week study with hypertensive patients, taking the antihypertensive drug nifedipine (a calcium channel blocker), plasma levels of endothelin 1 (the signaling molecule responsible for blood vessels narrowing) was significantly lowered by 20% in the Pycnogenol® group(6).

The concentration of a vasodilatory molecule (6-keto prostaglandin F1a), on the other hand, increased compared to the placebo group.

This is a clear indication of improved endothelial function.

A third double-blind, placebo-controlled study reported similar effects in hypertensive patients with type II diabetes, taking an anti-hypertensive drug, an ACE inhibitor together with 125 mg Pycnogenol® daily for 3 months(7). In this case, the serum endothelin-1 levels were

beneficial effects of Pycnogenol® on endothelial function in patients with cardiovascular diseases.

a calcium channel blocker (nifedipine), the effects of Pycnogenol® on blood pressure have been investigated(6). Every two weeks during the 12-week study, the individual nifedipine dosage was adjusted so that a blood pressure below 130 mmHg was achieved. 57% of the patients supplemented with Pycnogenol® were able to cut their individual nifedipine medication dosage by half to keep their blood pressure in a healthy range. In another study, Patients with metabolic syndrome criteria, such as obesity, hypertension, elevated blood sugar and high cholesterol, supplemented with Pycnogenol® for 6 months showed significant improvement of most parameters(15). Compared to a control group medicated with an ACE-inhibitor only, patients taking Pycnogenol® in addition achieved significantly improved blood pressure and

(10)

Stabilised blood pressure and normalised blood glucose and blood lipid profiles Elevated or high blood pressure (hypertension) increases the risk of cardiovascular problems, such as heart attack or stroke. Endothelial dysfunction favouring vasoconstriction is a common mechanism involved in hypertension-related cardiovascular events(13).

The improved endothelial function with Pycnogenol® leads to improved vessel relaxation, when needed, which, in turn, helps to normalise elevated blood pressure. This beneficial effect of Pycnogenol® was investigated in a doubleblind, placebo-controlled, crossover study with border-

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PHARMA PULSE better total blood cholesterol and HDL values. In another double-blind, placebo-controlled study, mentioned before, with type-II diabetic patients medicated with an ACE inhibitor, and hypoglycemic medication, blood pressure decreased significantly after Pycnogenol® supplementation(7).

Half of the patients were able to lower the dose of their individual hypotensive medication.

Additionally, Pycnogenol® supplementation was shown to lower fasting blood sugar levels by 16.7%, which was significant compared to the placebo group (7) . As high blood sugar is another high-risk factor for cardiovascular diseases, the antidiabetic effects of Pycnogenol® were further investigated. In the double-blind, placebo-controlled study by Ximing Liu and colleagues, Pycnogenol® was shown to lower blood glucose levels significantly compared to baseline and placebo by 16.1%(6).

A possible mechanism to understand how Pycnogenol® contributes to lower glucose blood levels is that sugar absorption was slowed down in patients supplemented with Pycnogenol® by inhibition of α-glucosidase, the enzyme that disassembles starch(16).

In addition to the sugar levels in the blood, Pycnogenol® was found to improve the blood lipid profile as well, by lowering LDL cholesterol and increasing HDL cholesterol. Young and healthy subjects, supplemented with Pycnogenol® for 6 weeks, showed a significantly improved blood lipid profile, with increased HDL cholesterol by 11% and lowered LDL cholesterol by 7%(17). The study with type-II diabetic patients found a reduction by 12% of LDL cholesterol after 3 months of supplementation with Pycnogenol®, which was significantly lower than the levels of the placebo group(7). The HDL cholesterol levels were not investigated in this study.

Similar effects were observed in a study with patients treated with Pycnogenol® for venous insufficiency(18). After taking Pycnogenol® for 4 weeks, total cholesterol blood levels decreased by 20%, LDL cholesterol decreased by 13%

62 EXPRESS PHARMA September 2021

and HDL cholesterol increased by 11%. In 21 men, supplementation with Pycnogenol® over a period of 3 months significantly lowered both total cholesterol and LDL by 8% and 19.2%, respectively(19). A similar, double blind, placebo-controlled study with 53 men showed a decrease of total and LDL cholesterol by 20% and 21%, respectively(20). In a double-blind, placebo-controlled clinical trial with 200 peri-menopausal women, a significant decrease of LDL cholesterol by 9.9% and a significant increase of HDL cholesterol by 4.6% were observed after 6 months of Pycnogenol® supplementation(21). A controlled 6-month study with patients suffering from meta-

under the skin, the diameter of micro vessels in fingernails, as well as the blood flow velocity were measured to investigate the effects of Pycnogenol® on microcirculation in patients with microangiopathy resulting from chronic artery diseases, diabetes or chronic venous insufficiency(24-28). The increase in diameter of micro vessels at the fingertips was much higher in Pycnogenol® supplemented patients than in the control group, all suffering from a coronary artery disease (24) . Patients with diabetic microangiopathy, who took Pycnogenol® for 6 weeks had better oxygenised tissues, whereas the carbon dioxide levels were decreased compared with con-

Normalised platelet activity

bolic syndrome was conducted to investigate the effect of Pycnogenol® supplementation on central obesity, elevated triglycerides, low HDL cholesterol, high blood pressure and fasting blood glucose(22). A daily intake of 150 mg Pycnogenol® significantly decreased waist circumference, triglyceride levels (by 24.3%), blood pressure and increased the HDL cholesterol levels by 25.7% in men and 24.5% in women.

trol patients(25, 26). A healthy microcirculation is tightly connected to vascular permeability and capillary filtration.

Pycnogenol® was demonstrated to improve retinal microcirculation and to help capillary filtration and the resulting edema in a clinical study with diabetic patients suffering from retinopathy(27). Retinal edema, assessed by measuring the retinal thickness, was significantly reduced in patients taking Pycnogenol®. This study suggested that Pycnogenol® can counteract enhanced capillary filtration leaking by improving microcirculation. Another measure for capillary leaking is the rate of ankle swelling, which was significantly reduced after supplementation with Pycnogenol® in diabetic patients with microangiopathy(28).

cardiovascular patients taking aspirin confirmed that Pycnogenol® intake does not further decrease platelet activity (5) . In another study, Pycnogenol® prevented platelet hyperactivity in heavy smokers but did not influence bleeding time, as compared to a group taking aspirin, in which the time of bleeding was significantly increased from 167 to 236 seconds(30).

Improved microcirculation Insufficient microcirculation can contribute to cardiovascular disease as well as hypertension or diabetes(23). Pycnogenol® has been shown to improve the microcirculation perfusion system(24-28). In several clinical studies, the levels of oxygen and carbon dioxide in the tissues

Blood platelet activation and aggregation can lead to severe conditions such as thrombosis, stroke or heart attack. Pycnogenol® showed to lower blood platelet aggregation by increasing the production of endothelial NO(29,30). In healthy smoking individuals, who have pathologically increased blood platelet activity, Pycnogenol® has been shown to reduce platelet aggregation to the level of non-smokers after supplementation with Pycnogenol® for 2 months(29). However, normal platelet function was not further decreased in healthy non-smokers. A double-blind placebo-controlled study with

ter 5 days of daily intake, Pycnogenol® significantly prevented the up-regulation of 5LOX and COX-2 (pro-inflammatory enzymes)(32) In another ex vivo study, plasma samples of volunteers after intake of Pycnogenol® showed statistically significantly inhibited NF-kB activation by 15.5% and matrix metalloproteinase 9 (MMP-9) release by 25%, two important regulators in the inflammation process(33). In a similar study, statistically significant, but non selective, inhibition of inflammatory molecules COX-1 and COX- 2 was observed after intake of 300 mg Pycnogenol® (34).

Pycnogenol® French maritime pine bark extract is a safe,

natural and evidence-based solution to efficiently support cardiovascular health. It has potent anti-inflammatory effects and helps improve blood pressure, endothelial function, microcirculation and platelet activity, as well as blood lipid and sugar profiles.

For more information on this cardiovascular multitasker, please visit www.pycnogenol.com

Controlled inflammation Although inflammation can be beneficial and has evolved to promote survival, chronic inflammation was found to be a key mechanism driving atherosclerotic cardiovascular diseases(31). Pycnogenol® has potent anti-inflammatory activity, shown in several studies(32-34). A study showed that af-

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2. Mendis S, Puska P, Norrving B, World Health Organization.,

PHARMA PULSE World Heart Federation., World Stroke Organization. Global atlas on cardiovascular disease prevention and control. Geneva: World Health Organization in collaboration with the World Heart Federation and the World Stroke Organization; 2011. vi, 155 p. p.

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4. Fitzpatrick DF, Bing B, Rohdewald P. Endothelium-dependent vascular effects of Pycnogenol. J Cardiovasc Pharmacol. 1998;32(4):509-15.

5. Enseleit F, Sudano I, Periat D, Winnik S, Wolfrum M, Flammer AJ, et al. Effects of Pycnogenol on endothelial function in patients with stable coronary artery disease: a double-blind, randomized, placebo-controlled, cross-over study. Eur Heart J. 2012;33(13):1589-97.

6. Liu X, Wei J, Tan F, Zhou S, Wurthwein G, Rohdewald P. Pycnogenol, French maritime pine bark extract, improves endothelial function of hypertensive patients. Life Sci. 2004;74(7):85562.

7. Zibadi S, Rohdewald PJ, Park D, Watson RR. Reduction of cardiovascular risk factors in subjects with type 2 diabetes by Pycnogenol supplementation. Nutr Res. 2008;28(5):315-20.

8. Uhlenhut K, Högger P. Facilitated cellular uptake and sup-

pression of inducible nitric oxide synthase by a metabolite of maritime pine bark extract (Pycnogenol). Free Radic Biol Med. 2012;53(2):305-13.

9. Hu S BG, Cornelli U, et al Effects of Pycnogenol® on endothelial dysfunction in borderline hypertensive, hyperlipidemic, and hyperglycemic individuals: the borderline study. Int Angiol 2015;34(1):43-52.

10. Strijdom H, Chamane N, Lochner A. Nitric oxide in the cardiovascular system: a simple molecule with complex actions.

Cardiovasc J Afr. 2009;20(5):303-10.

11. Sowers JR, Epstein M. Diabetes Mellitus and Associated Hypertension, Vascular Disease, and Nephropathy. Hypertension. 1995;26(6):869-79.

12. Mudau M, Genis A, Lochner A, Strijdom H. Endothelial dysfunction: the early predictor of atherosclerosis. Cardiovasc J Afr. 2012;23(4):222-31.

13. Konukoglu D, Uzun H. Endothelial Dysfunction and Hypertension. Adv Exp Med Biol.

2017;956:511-40.

14. Hosseini S LJ, Sepulveda RT, Rohdewald P, Watson RR. A randomized, double-blind, placebo-controlled, prospective, 16 week crossover study to determine the role of Pycnogenol in modifying blood pressure in mildly hypertensive patients.

Nutr Res. 2001;21(9):1251-60.

15. Stuard SBG, Cesarone, M.R., Ricci, A., Dugall, M., Cornelli, U., Gizzi, G. Pellegrini L, Rohdewald, P.J. Kidney function in metabolic syndrome may be improved with Pycnogenol. Pan-

minerva Med. 2010;52(2):27-32.

16. Schäfer A, Högger P. Oligomeric procyanidins of French maritime pine bark extract (Pycnogenol) effectively inhibit alpha-glucosidase. Diabetes Res Clin Pract.

2007;77(1):41-6.

17. Devaraj S V-LS, Kaul N, Schönlau F, Rohdewald P, Jialal I. Supplementation with a pine bark extract rich in polyphenols increases plasma antioxidant capacity and alters plasma lipoprotein profile. Lipids.

2002;37(10):931-4.

18. Koch R. Comparative study of Venostasin and Pycnogenol in chronic venous insufficiency.

Phytother Res. 2002;16 Suppl 1:S1-5.

19. D?ura?ková Z, Trebatický B, Novotný V, it?anová I, Breza J. Lipid metabolism and erectile function improvement by pycnogenol®, extract from the bark of pinus pinaster in patients suffering from erectile dysfunction-a pilot study. Nutrition Research.

2003;23(9):1189-98.

20. Trebaticky B, Muchova J, Ziaran S, Bujdak P, Breza J, Durackova Z. Natural polyphenols improve erectile function and lipid profile in patients suffering from erectile dysfunction.

Bratisl Med J. 2019;120(12):941 4.

21. Yang HM, Liao MF, Zhu SY, Liao MN, Rohdewald P. A randomised, double-blind, placebocontrolled trial on the effect of Pycnogenol on the climacteric syndrome in peri-menopausal women. Acta Obstet Gynecol Scand. 2007;86(8):978-85.

22. Belcaro G, Cornelli U, Luzzi R, Cesarone MR, Dugall M, Feragalli B, et al. Pycnogenol(R) supplementation improves health risk factors in subjects with metabolic syndrome. Phytother Res. 2013;27(10):1572-8.

23. Mili?i? D, Jakuš N, Fabijanovi? D. Microcirculation and Heart Failure. Curr Pharm Des. 2018;24(25):2954-9.

24. Wang S, Tan D, Zhao Y, Gao G, Gao X, Hu L. The effect of Pycnogenol® on the microcirculation, platelet function and ischaemic myocardium in patients with coronary artery diseases.

European Bulletin of Drug Research. 1999;7(2):19-25.

25. Belcaro G, Cesarone MR, Errichi BM, Ledda A, Di Renzo A, Stuard S, et al. Diabetic ulcers: microcirculatory improvement and faster healing with pycnogenol. Clin Appl Thromb Hemost. 2006;12(3):318-23.

26. Belcaro G. LR, Dugall M., Ippolito E., Saggino A. Venous ulcers: Microcirculatory improvement and faster healing with local use of Pycnogenol®. Angiology. 2005;56(6):699-705.

27. Steigerwalt R, Belcaro G, Cesarone MR, Di Renzo A, Grossi MG, Ricci A, et al. Pycnogenol improves microcirculation, retinal edema, and visual acuity in early diabetic retinopathy. J Ocul Pharmacol Ther.

2009;25(6):537-40.

28. Cesarone MR, Belcaro G, Rohdewald P, Pellegrini L, Ledda A, Vinciguerra G, et al. Improvement of diabetic microangiopathy with pycnogenol: A prospective, controlled study.

Angiology. 2006;57(4):431-6.

29. Araghi-Niknam M, Hosseini, S, Larson, D, Rohdewald, P and watson, RR. Pine bark extract reduces platelet aggregation.

Integrative Medicine.

1999;2(2/3).

30. Pütter M GK, Würthwein G, Araghi-Niknam M, Watson RR, Hosseini S, Rohdewald P. . Inhibition of smoking-induced platelet aggregation by Aspirin and Pycnogenol. Thrombosis Research 1999;55:155-61.

31. Alfaddagh A, Martin SS, Leucker TM, Michos ED, Blaha MJ, Lowenstein CJ, et al. Inflammation and cardiovascular disease: From mechanisms to therapeutics. American Journal of Preventive Cardiology.

2020;4.

32. Canali R, Comitato R, Schonlau F, Virgili F. The antiinflammatory pharmacology of Pycnogenol in humans involves COX-2 and 5-LOX mRNA expression in leukocytes. Int Immunopharmacol.

2009;9(10):1145-9.

33. Grimm T, Chovanova Z, Muchova J, Sumegova K, Liptakova A, Durackova Z, et al. Inhibition of NF-kappaB activation and MMP-9 secretion by plasma of human volunteers after ingestion of maritime pine bark extract (Pycnogenol). J Inflamm (Lond). 2006;3:1.

34. Schäfer A, Chovanova Z, Muchova J, Sumegova K, Liptakova A, Durackova Z, et al. Inhibition of COX-1 and COX-2 activity by plasma of human volunteers after ingestion of French maritime pine bark extract (Pycnogenol). Biomed Pharmacother. 2005;60(1):5-9.

EXPRESS PHARMA

63

September 2021

PHARMA PULSE

Gandhi Automations' High Speed Doors The doors are manufactured with European collaboration and technology with innovative and creative engineering

H

igh Speed Doors (HSDs) designed and manufactured by Gandhi Automations are sturdy and dependable, and are the ideal solution for medium and large entrances. The doors are manufactured with European collaboration and technology with innovative and creative engineering.

Fast-moving functional and reliable doors are needed in industrial and commercial contexts. Gandhi-designed and manufactured High Speed Doors are versatile and solid, ensuring long-lasting reliability.

The modular structure of the curtains, assembled and joined by anodized aluminium extrusions, provides for a wide range of polyester sections available in a variety of colours. Wide, full-width window panels ensure a safer traffic and allow more light in. Their fast and easy replacement, in case of accidental tearing, saves money and time. The alternating metal tubular structure there inserted ensures high wind-resistance.

Prime High Speed Doors are the ideal solution for internal and external entrances and effectively operate in any situation, even when strong winds are blowing, and in rooms with high volume traffic. Sturdy and dependable, Prime is the intelligent door for medium and large entrances.

High Speed Doors for external entrance are equipped with spring steel wind lock in curtain pocket that ensures silent door travel, higher wind loads and curtain stability.

time of transition from one facility to another, avoiding any human error which can cause damage to the High Speed Door and all this can be achieved due to the innovative anti-crash. Gandhi Automations provides a world-class product with great security.

Below are the features of selfrepairing High Speed Doors offered by Gandhi Automations:◆ Flexible and Self-Repairing Door ◆ Functional, safe, quick and resistant ◆ Innovative anti-crash system ◆ Can be equipped with PVC vision windows ◆ Self-lubricating maintenance free guide ◆ Smooth and silent opening and closing ◆ Protects traction unit, enables rapid wiring and safety photocell ◆ Flexible curtain in self-extinguishing material ◆ Self-resetting without intervention ◆ Quickly back to operation ◆ Control panel designed for an intensive continuous service

High Speed Door - Prime Reset It is a unique High Speed SelfRepairing Door with the latest technology that prevents downtime of the door system.

In case, the curtain is impacted accidentally, it will cause the curtain to move out of the guides without damage. The

64 EXPRESS PHARMA September 2021

movement of the door is designed in such a way that it can be recovered with a simple opening and closing operation.

Gandhi Automations manufactures doors of the highest quality that meet the issue for greater flexibility desired by

clients. High Speed Self-Repairing Door in PVC is the most suitable solution in the field industries. It lowers the

For further details, contact: Gandhi Automations Pvt Ltd Chawda Commercial Centre Link Road, Malad (W) Mumbai - 400064, India Off: +91 22 66720200 / 66720300(200 Lines) Fax: +91 22 66720201 Email: sales@geapl.co.in Website: www.geapl.co.in

PHARMA PULSE

Fast performance,extreme durability in weighing applications Mettler Toledo's XSR precision balances were conceptualised to simplify workflows while maintaining accuracy. Their robust design protects against dust and dirt, and a built-in notepad reduces time spent on data handling and transfer - improving repeatability, reducing risk of errors, and promoting long life

W

ithout good data, scientific advance is impossible. Academic laboratories thus depend on reliable measuring equipment that generates precise and accurate results, and simplifies their export for recordkeeping or further analysis.

Mettler Toledo's XSR Precision Balances meet researchers' needs easily, ensuring accuracy, lasting performance and maximum efficiency.

Along with the latest in high-performance weighing sensors, the XSR balance features SmartPan™, an innovative weighing pan that eliminates the effects of air turbulence. Improved sample stabilisation yields results up to twice as fast as a standard weighing pan; high-quality data can be achieved in almost any environment.

The XSR balance's robust design also includes overload protection to safeguard the weighing cell. In addition, integrated StatusLight™ and LevelControl functionalities ensure that measurements are not made unless the balance is ready to weigh, while customisable tolerance profiles and MinWeigh warnings notify users when inappropriate actions are taken.

Further, manual reporting is a thing of the past. Task parameters and results displayed on the integrated notepad can quickly be transferred to PC via USB or Ethernet, eliminating transcription errors. As lab work can be repetitive, the XSR was conceptualised to provide a

mounted protective cover, which, combined with the full metal housing, protects the XSR against dust, dirt, liquids and harsh chemicals. Smooth surfaces and dishwasherproof parts make the entire balance easy to clean, while rugged construction limits its repair costs. Delivering reliable weighing performance, and with clever features to support efficient, consistent data-generation, XSR Precision Balances are a truly ergonomic solution to researchers' needs - and to furthering scientific progress.

For more details, visit: www.mt.com/xsr-precision

Mettler Toledo's XSR Precision Balances meet researchers' needs easily, ensuring accuracy, lasting performance and maximum efficiency

comfortable weighing experience. A high-resolution colour display makes figures easy to read; the glove-compatible screen ensures accurate and

fast touch response. Moreover, ErgoStand™ allows standing operators to adjust the screen to reduce neck strain. XSR Precision Bal-

ances are made to last. To prolong balance life, the design simplifies maintenance.

The terminal is fully detachable and has a pre-

(Mettler Toledo is a leading global manufacturer of precision instruments. The company is the world's largest manufacturer and marketer of weighing instruments for use in laboratory, industrial and food retailing applications. The company also holds top-three market positions for several related analytical instruments and is a leading provider of automated chemistry systems used in drug and chemical compound discovery and development. In addition, the company is the world's largest manufacturer and marketer of metal detection systems used in production and packaging. Additional information about Mettler Toledo is available at www.mt.com).

Email us at sales.sales@mt.com Call us toll-free at 1800 22 8884 & 1800 1028 460

EXPRESS PHARMA

65

September 2021

PHARMA PULSE

Virosil Pharma: Arevolutionary,eco-friendly fumigant Virosil Pharma has proved to be effective in controlling aerial bacteria and fungus present in sterile rooms.The area becomes completely sterile within 60 minutes of spraying without causing any irritation to the eyes, nose and skin - unlike conventionally used formulations ABSTRACT In the past years, the pharma and healthcare industry has witnessed tremendous growth and there have been tie-ups with a number of multinationals for production and R&D facilities to be nurtured in India.

Organisations are applying for ISO standards and upgrading themselves to the latest norms related to health and hygiene.

Microbial contamination and pollution play a significant role in the pharmaceutical industries. Control of microbes has always been the biggest challenge to these industries.

A load of microbes are present in areas such as production, storage/packaging, R&D, Q.A/Q.C., filling etc. They are present everywhere in the air, surface, water, instruments, linens etc.

Hence the disinfectant used should be so precise that it should not only take care of the microbial contamination but also be user and eco-friendly.

Virosil Pharma meets all the required standards for the pharmaceutical industry.

strict regulations imposed by European Health bodies.

PRODUCT DISCRIPTION Virosil Pharma is a multicomponent fumigant and disinfectant. The oxidizing agent used is hydrogen peroxide, which is bonded with stabilizing agents to form a complex solution. A long-lasting effect is ensured by the addition of silver, which acts as a catalyst in trace amounts. The bactericidal effect of silver is based on the fact that the monovalent silver

ion Ag+ binds very firmly to bacterial proteins by a covalent or co-ordinate bond, and thus inactivates or precipitates these. ◆ Its effectiveness against bacteria, viruses, amoebae, fungi and algae; i.e. its extremely wide range of application makes it easy to handle for the end user; i.e. only one product is needed, where so far 2, 3 or various products were necessary. ◆ Owing to the good stability of the product, a long storage

66 EXPRESS PHARMA September 2021

Clean Area Classification

Microbial limit Cfu / 10 cu.ft.

Microbial limit Cfu / 10 cu.m.

100

< 1a

< 3a

1000

<2

<7

10,000

<5

< 18

100,000

<25

<88

a = samples from class 100 environments should normally yield no microbiological contaminants

WHO 2002 MICROBIAL LIMITS Grade

Max. no. of microorganisms permitted / m3

A

Less than 1

B

5

C

100

D

500

EU GMP 2002

ABOUT US Sanosil Biotech, a Mumbaibased company, has launched a range of multipurpose disinfectants which are eco-friendly, chlorine-free and completely biodegradable and have applications in the pharma and healthcare industry as well as in the food processing industry.

It is manufactured in India in technical collaboration with SANOSIL AG of Switzerland.

SANOSIL AG in Switzerland is the patent holder and has joint venture agreements in more than 15 countries such as France, Italy, Spain, Holland, Norway, South Africa, Australia, Saudi Arabia, Oman, the UAE, etc. The product is being used in various countries by reputed institutions and has been thoroughly tested under

USFDA DRAFT GUIDELINES

ADVANTAGES

PROPERTIES

# Eco- friendly - It is totally biodegradable since (H2O2) breaks down into water & oxygen # Chlorine free # Non-toxic (no irritation to skin or eyes # No effect on pH # Non carcinogenic and non mutagenic # Excellently rinseable with no remains

# Can easily be dosed # Does not foam # Decomposes into water and oxygen # It is excellently rinseable with no remains # Treats any other material with consideration

Grade

Air sample cfu / cu.m.

Settle plates (90mm) cfu / 4 hours

Contact plate 55mm cfu / plate

Glove print Cfu/glove

A

<1

<1

<1

<1

B

10

5

5

5

C

100

50

25

-

D

200

100

50

-

time can be guaranteed. As the product remains stable at high water/air temperatures, and as its effectiveness is even increased at high temperatures. ◆ Due to its long-term effectiveness and pronounced characteristics to prevent recontamination, this product is perfectly suited for disinfection of drinking water and wells. ◆ Virosil Pharma is ecologically harmless. Its principal constituent - hydrogen peroxide - does not pollute waste wa-

ter, because it breaks down into water and oxygen (H2O and O2), i.e. it produces no noxious by-products. ◆ The two basic substances (H2O2 and Ag) enhance their advantages (*synergism). The bactericidal effect comes into action quicker and more intensively than if either substance was used on its own.

Fumigation with Virosil Pharma, the perfect Salternative to Formalin Fumigation is one of the most

PHARMA PULSE important factors associated with pharma industries, it plays a vital role in maintaining the sterility of areas and is directly related to production.

Sanosil Biotech is the first company to pioneer the novel concept of eco-friendly fumigation. The company has great respect for human health and the environment. The CEO, Dev Gupta, an MBA from the Bentley Graduate School of Business, Boston, has been actively marketing the brand nationally. According to Gupta, "Virosil Pharma has simplified the lives of so many people who work in the pharmaceutical industry as they are guaranteed sterility with the minimum risk exposure". As there was a high risk to the staff involved in the use of Formaldehyde/Glutraldehyde for sterilization and disinfection.

Owing to the stringent integrated micro contamination control and biosafety requirements, it is desirable to have micro-contamination control procedures and methods that could be monitored, evaluated and assessed periodically, which are convenient, cost-effective and safe.

A glimpse at the standards put down by various would monitoring agencies would help an individual or an organization help decide on choosing the most appropriate control procedure/methods. The important microbial limits which have been prescribed by various agencies is as follows: To meet those requirements aerial disinfection (fumigation) with formaldehyde was the most convenient method. With the regulatory having restricted the use of formaldehyde and also putting into place the monitoring levels of formaldehyde after fumigation makes it a procedure with its own limitations.

Formaldehyde is a known carcinogen (IARC & NTP).

Formalin is toxic by inhalation, toxic if swallowed, may be fatal if swallowed, causes eye burns, may cause blindness, strong sensitizer, causes irritation to skin, eyes, and respiratory tract. Repeated or prolonged exposure increases the cancer risk.

COMPARISON VIROSIL PHARMA

FORMALIN

Eco-friendly, Non-toxic

Highly toxic

Room gets sterilized within 1 hour after fumigation

Requires overnight fumigation

Requires no de-fumigation

Requires de-fumigation

Person can be present during fumigation

Causes skin, eye irritation even after next day of fumigation

Time Saving

Time consuming

Multiple Applications

Application restricted

Virosil Pharma has been a direct alternative to Formalin Fumigation. Virosil Pharma has proved to be effective in controlling aerial bacteria and fungus present in sterile rooms. The area becomes completely sterile within 60 minutes of spraying without causing any irritation to the eyes, nose and skin - unlike conventionally used formulations. Virosil Pharma can even be successfully used in AHU which are responsible for optimal and steady air exchange in production facility, of which the ducts, air shafts, humidificator, filters, etc. are often contaminated with loads of bacterial and bio-films.

The main aim of Virosil Pharma is to increase productivity by cutting down disinfection time while at the same time providing a totally microbe-free environment.

Virosil Pharma is also very effective in disinfection of all critical surfaces that come in contact with pharma products.

There is no requirement to rewash equipment and surfaces disinfected with Virosil Pharma since it is H2O2 based and decomposes into water and oxygen.

Virosil Pharma has been tested by several reputed and renowned institutions in India with respect to its disinfection and fumigation applications in Pharmaceutical Industry Because of all these factors, Virosil Pharma has attained maximum satisfaction of the customers in controlling the microbial contamination in their respective applications.

The introduction of an ecofriendly, non-carcinogenic and totally biodegradable versatile product, like Virosil Pharma,

A GRAPHICALVIEW ON DISINFECTANT EVALUATION DATA - VIROSIL PHARMA

Organism Type S.AUR

B.CER

E.COLI

P.AER

C.ALB

2.50%

429.83

397.4

418.15

289.38

0

3.00%

514.44

502.4

440.92

349.48

0

4.00%

615.44

683.14

490.625

404.5

0

5.00%

669.32

1063.07

580.77

452.16

0

has not only brought an end to the era of conventional biocides but has completely solved the disinfection requirements which these healthcare industries were prone to.

Targets Sanosil Biotech is marketing this disinfectant under the 'Virosil Pharma' brand name and is targeting the entire industrial belt of India. The com-

pany has already set up a distribution and infrastructure network having establishments in Maharashtra, M.P., Hyderabad, Chennai and Delhi.

EXPRESS PHARMA

67

September 2021

PHARMA PULSE

Major challenges in pharmaceutical industry Rutuja Sonawane, Officer- Sales and Marketing, Ami Polymer, explains how the products offered by the company can help meet the challenges faced by the pharmaceutical industry

T

he pharmaceutical industry has been successful for decades.

Yet, a few challenges exist in the industry. Let's examine these.

The increasing accessibility to healthcare services has opened the doors for the pharmaceutical industry players to broaden their target market. Such emerging markets are becoming crucial for pharmaceutical companies. As we all know, India is the largest provider of generic drugs globally, the

As the pharmaceutical industry becomes increasingly complex and globalized, the sector must become more cost-efficient

vital role during pharma and biopharma drug manufacturing activities which influence the quality of the drug product. Consumables covered include raw materials, excipients, APIs, packaging materials, drug products and polymeric and single-use components items. Apart from these items, there are many items which are directly or indirectly used in manufacturing activities, which is directly related to the integrity of the drug product. These items are so-

called consumables or miscellaneous materials.

What are consumables?

Key materials which are used in support of manufacturing, or which is coming in contact with the product during manufacturing that may not become part of the final product.

The consumables can be classified into three categories based on their applications.

Direct quality impacting: Consumables which will have direct contact with product and directly affect the qual-

Ami Polymer product portfolio

Vital challenges for managing consumable materials in pharma sector

nation enjoys an important position in the global pharma sector. Therefore, the future of Indian pharma industry is quite bright, but there are a few dark clouds on the horizon as well.

As the pharmaceutical industry becomes increasingly complex and globalised, the sector must become more cost-efficient.

There have been several speculations about the stationary growth of the pharmaceutical industry, but recent technological advancements are expected to encourage the growth of this industry in the years to come.

Consumables items play a

68 EXPRESS PHARMA September 2021

COVID-19 impact

The polymer tubings used for the application of fluid transfer, filtration, connection flow control and single use system (SUS)

ity, purity, strength and safety of the final product.

Examples are product filters, product contact tubing, single-use assemblies and process gases, polyethylene bags, etc.

Indirect quality impacting: Consumables which do not come into direct contact with the product and may affect the quality, purity, strength and safety of the product. Examples are gloves, garments, lubricants, wipes/mops, etc.

Non-quality impacting: Consumables which will not affect the quality, purity, strength and safety of the product. Examples are engineering tools and housekeeping items, etc.

Key challenges in pharma and biopharmaceutical industry ◆ Demand forecasting ◆ Reduced demand for prescription medicine ◆ A lack of a stable pricing and policy environment (price fluctuation assessment) ◆ Risk management ◆ Loss of exclusivity ◆ Cyber security threats Ami Polymer provides end-to-end solution to pharma and biopharma industries for direct quality impacting consumables.

The company is the manufacturer of tubings, singleuse assembly and other polymeric materials with superior quality and standard, ensuring the product integrity as these consumablesare directly used in contact with the product.

If you have any query, please contact: tubing@amipolymer.com Tubing and SUS validation packs available upon request. www.amipolymer.in (Vinay.p@amipolymer.com and Anuj.s@amipolymer.com

REGD.WITH RNI NO. MAHENG/2005/21398, POSTAL REGD. NO. MCS/164/2019 – 21, PUBLISHED ON 5TH EVERY MONTH, POSTED ON 9TH, 10TH, AND 11TH EVERY MONTH POSTED AT MUMBAI PATRIKA CHANNEL SORTING OFFICE, MUMBAI – 400001